Chiral N-heterocyclic carbene-copper(I)-catalyzed asymmetric allylic arylation of aliphatic allylic bromides: Steric and electronic effects on γ-selectivity

Article abstract of DOI:10.1021/jo102386s

Chiral N-heterocyclic carbene ligands were electronically and sterically tuned to improve γ-selectivity in copper(I)-catalyzed asymmetric allylic arylation of aliphatic allylic bromides with several aryl Grignard reagents. High γ-selectivity was realized

Full text of DOI:10.1021/jo102386s

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Chiral N-Heterocyclic Carbene-Copper(I)-Catalyzed
Asymmetric Allylic Arylation of Aliphatic Allylic Bromides:
Steric and Electronic Effects on γ-Selectivity
Khalid B. Selim,† Hirotsugu Nakanishi,‡ Yasumasa Matsumoto,‡ Yasutomo Yamamoto,§
Ken-ichi Yamada,‡ and Kiyoshi Tomioka*,‡,§
†Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University,
Mansoura 35516, Egypt, ‡Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida,
Sakyo-ku, Kyoto 606-8501, Japan, and §Faculty of Pharmaceutical Sciences, Doshisha Women’s College of
Liberal Arts, Kodo, Kyotanabe 610-0395, Japan
tomioka@pharm.kyoto-u.ac.jp
Received December 3, 2010
Chiral N-heterocyclic carbene ligands were electronically and sterically tuned to improve γ-
selectivity in copper(I)-catalyzed asymmetric allylic arylation of aliphatic allylic bromides with
several aryl Grignard reagents. High γ-selectivity was realized when either the aryl group of the
Grignard reagent or the aryl group on the N-substituent of the carbene ligand was electron-deficient
or when either the carbene ligand or allylic bromide was bulky. The results indicated that electron
deficiency and steric hindrance of the initially formed σ-allyl copper intermediate enhance the rate of
the reductive elimination to give γ-products as major isomers.
Introduction
of the substrates and chiral catalyst, as well as the reagent
reactivity. Many reports have documented powerful meth-
ods to control the regio- and enantioselectivities of the
reaction products with alkyl coppers derived from alkyl
Grignard or dialkylzinc reagents using different types of
chiral ligands.3,4 The power of these catalysts, however,
remains insufficient for less reactive aryl, alkenyl, and alky-
nyl anions.5,6 Hoveyda recently reported efficient chiral
Among transition metal-catalyzed allylic substitutions,1 a
method using a chiral copper catalyst with hard nucleophiles
is a potentially useful asymmetric C-C bond-forming
reaction.2 Regioselectivity and enantioselectivity, however,
are greatly affected by the structural and electronic features
(1) (a) Trost, B. M.; Lee, C. In Catalytic Asymmetric Synthesis, 2nd ed.;
Ojima, I., Ed.; Wiley: New York, 2000; p 593. (b) Helmchen, G. In
€
Asymmetric Synthesis;The Essentials; Christmann, M., Brase, S., Eds.;
(4) Copper-mediated γ-selective allylic substitution using directing leav-
ing groups: (a) Breit, B.; Schmidt, Y. Chem. Rev. 2008, 108, 2928–2951.
(b) Kiyotsuka, Y.; Kobayashi, Y. J. Org. Chem. 2009, 74, 7489–7495. , and
references therein.
Wiley-VCH: Weinheim, Germany, 2007; pp 95-99.
€
€
(2) Karlstrom, A. S. E.; Backvall, J. E. In Modern Organocopper Chem-
istry; Krause, N., Ed.; Wiley-VCH: Weinheim, Germany, 2001; p 259.
(3) Recent reviews in Cu-catalyzed asymmetric allylic substitution:
(5) (a) Tseng, C. C.; Paisley, S. D.; Goering, H. L. J. Org. Chem. 1986, 51,
€
ꢀ
ꢁ
€
2884–2891. (b) Backvall, J. E.; Persson, E. S. M.; Bombrun, A. J. Org. Chem.
1994, 59, 4126–4130.
(6) A maximum of 30% ee has been achieved in Cu-catalyzed AAAr using
aryl Grignard reagent: (a) Meuzelaar, G. J.; Karlstrom, A. S. E.; Van
(a) Alexakis, A.; Backvall, J. E.; Krause, N.; Pamies, O.; Dieguez, M. Chem.
Rev. 2008, 108, 2796–2823. (b) Harutyunyan, S. R.; den Hartog, T.; Geurts,
K.; Minnaard, A. J.; Feringa, B. L. Chem. Rev. 2008, 108, 2824–2852.
(c) Falciola, C.; Alexakis, A. Eur. J. Org. Chem. 2008, 3765–3780.
(d) Alexakis, A.; Malan, C.; Lea, L.; Tissot-Croset, K.; Polet, D.; Falciola,
C. Chimia 2006, 60, 124–130. (e) Yorimitsu, H.; Oshima, K. Angew. Chem.,
Int. Ed. 2005, 44, 4435–4439. (f) Kar, A.; Argade, N. P. Synthesis 2005, 2995–
3022. (g) Hoveyda, A. H.; Hird, A. W.; Kacprzynski, M. A. Chem. Commun.
2004, 1779–1785.
€
Klaveren, M.; Persson, E. S. M.; Del Villar, A.; van Koten, G.; Backvall, J. E.
Tetrahedron 2000, 56, 2895–2903. (b) Alexakis, A.; Malan, C.; Lea, L.;
Benhaim, C.; Fournioux, X. Synlett 2001, 927–930. (c) Seo, H.; Hirsch-Weil,
D.; Abboud, K. A.; Hong, S. J. Org. Chem. 2008, 73, 1983–1986. (d) Falciola,
C. A.; Alexakis, A. Chem.;Eur. J. 2008, 14, 10615–10627.
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Published on Web 01/25/2011
DOI: 10.1021/jo102386s
r
2011 American Chemical Society

Selim et al.
JOCArticle
SCHEME 1. Possible Pathway to R- and γ-Products in AAAr
with Chiral NHC-Cu Catalysts
FIGURE 1. Chiral N-heterocyclic carbene-copper(I) complexes.
bidentate N-heterocyclic carbenes (NHCs) for allylic sub-
stitution with aryl copper reagents derived from diarylzincs7
and aryldialkylaluminums,8 as well as alkenyl copper re-
agents derived from vinylaluminums.9 Nonetheless, signifi-
cant approaches using aryl Grignard reagents under copper-
catalyzed allylic substitution have yet to be developed.10
Recently, we introduced the first successful copper-cata-
lyzed asymmetric allylic arylation (AAAr) of aliphatic allylic
substrates with aryl Grignard reagents in the presence of
a chiral amidophosphane ligand.11 Further, highly enantio-
selective and γ-selective copper-catalyzed allylic arylation of
cinnamyl bromides was achieved using an air-tolerant mono-
dentate chiral NHC12-CuCl catalyst 1 with aryl Grignard
reagents, in which the γ-selectivity was improved (up to 99%
yield, 97% γ-selectivity, and 98% ee) by steric tuning of the
catalyst, i.e., from 1a to 1b (Figure 1).13 The primary merit of
this method is its compatibility with several aryl Grignard
reagents, which are generally less reactive and less regiose-
lective toward allylic substrates, in addition to the easy
preparation of the NHC-copper catalysts from imidazoli-
nium salts and CuCl. In the reaction of an aliphatic substrate
hex-2-enyl bromide with PhMgBr, however, the enantio-
selectivity of the γ-product was unsatisfactory (74% ee),
despite its high yield (98%) and high γ-selectivity (91% γ-
product). Having achieved this allylic arylation, we next
directed our attention to enhance the selectivity of the
reaction toward aliphatic allylic substrates using a sterically
and/or electronically tuned monodentate chiral NHC-cop-
per catalyst.
Herein, we report a γ-selective AAAr of aliphatic allylic
bromide using aryl Grignard reagents under the catalysis of
NHC-copper(I) complexes, as well as steric and electronic
effects on the γ-selectivity.14 The reactions proceeded with
exceptional regioselectivity (up to 96:4) and high enantio-
selectivity (up to 96% ee), and transformations were com-
pleted within 0.5 h with a variety of aryl Grignard reagents
and 2.0 mol % of a chiral NHC-Cu complex 1a or 1f,
derived from commercially available and air-stable CuCl.
Results and Discussion
Working Hypothesis. Scheme 1 shows a possible pathway
of the formation of R- and γ-products based on previous
reports.15 First, the Grignard reagent undergoes transmeta-
lation with a Cu(I) complex to give arylcuprate I, which then
preferentially reacts with the allylic bromide in an SN20
fashion through the π-complex to form σ-allyl copper(III)
complex II.15e,f,h Reductive elimination of II produces the
γ-product, while isomerization of II into π-allyl complex III
leads to exclusive formation of the less sterically hindered
terminal σ-allyl complex IV, whose reductive elimination
gives the R-product. Therefore, the regioselectivity depends
on the relative rates of the reductive elimination of II and the
isomerization of II to IV and the following reductive elim-
ination. We speculated that increased steric hindrance or
electron deficiency in complex II promotes its reductive
elimination step, which liberates the copper from the steric
hindrance and electron deficiency, and improves γ-selec-
tivity.16,15d,15e,15h We thus tested the regio- and stereocon-
trolling ability of chiral NHC-Cu(I) complexes 1b-j bear-
ing N-benzhydryl groups with bulky or electron-deficient
(7) Kacprzynski, M. A.; May, T. L.; Kazane, S. A.; Hoveyda, A. H.
Angew. Chem., Int. Ed. 2007, 46, 4554–4558.
(8) Gao, F.; Lee, Y.; Mandai, K.; Hoveyda, A. H. Angew. Chem., Int. Ed.
2010, 49, 8370–8374.
(9) Lee, Y.; Akiyama, K.; Gillingham, D. G.; Brown, M. K.; Hoveyda,
A. H. J. Am. Chem. Soc. 2008, 130, 446–447.
(10) Ir-catalyzed AAAr with arylzinc reagents in high enantioselectivity
but moderate regioselectivity: (a) Alexakis, A.; El Hajjaji, S.; Polet, D.;
Rathgeb, X. Org. Lett. 2007, 9, 3393–3395. (b) Polet, D.; Rathgeb, X.;
Falciola, C. A.; Langlois, J.-B.; Hajjaji, S. E.; Alexakis, A. Chem.;Eur. J.
2009, 15, 1205–1216.
(11) Selim, K. B.; Yamada, K.; Tomioka, K. Chem. Commun. 2008, 5140–
5142.
(12) Our studies on chiral NHC: (a) Matsumoto, Y.; Yamada, K.;
Tomioka, K. J. Org. Chem. 2008, 73, 4578–4581. (b) Matsumoto, Y.; Selim,
K. B.; Nakanishi, H.; Yamada, K.; Yamamoto, Y.; Tomioka, K. Tetrahe-
dron Lett. 2010, 51, 404–406.
(13) Selim, K. B.; Matsumoto, Y.; Yamada, K.; Tomioka, K. Angew.
Chem., Int. Ed. 2009, 48, 8733–8735.
(15) Leading references: (a) Goering, H. L.; Singleton, V. D., Jr. J. Am.
Chem. Soc. 1976, 98, 7854–7855. (b) Levisalles, J.; Rudler-Chauvin, M.;
Rudler, H. J. Orgonomet. Chem. 1977, 136, 103–110. (c) Magid, R. M.
Tetrahedron 1980, 36, 1901–1930. (d) Goering, H. L.; Singleton, V. D., Jr.
J. Org. Chem. 1983, 48, 1531–1533. (e) Goering, H. L.; Kantner, S. S. J. Org.
Chem. 1984, 49, 422–426. (f) Corey, E. J.; Boaz, N. W. Tetrahedron Lett.
1984, 25, 3063–3066. (g) Keinan, E.; Bosch, E. J. Org. Chem. 1986, 51, 4006–
€
4016. (h) Backvall, J. E.; Sellen, M.; Grant, B. J. Am. Chem. Soc. 1990, 112,
6615–6621. (i) Goering, H. L.; Underiner, T. L. J. Org. Chem. 1991, 56, 2563–
€
2672. (j) Backvall, J. E.; Persson, E. S. M.; Bombrun, A. J. Org. Chem. 1994,
59, 4126–4130. (k) Persson, E. S. M.; van Klaveren, M.; Grove, D. M.;
(14) Cu-catalyzed AAA using monodentate NHC and alkyl Grignard
reagents: (a) Tominaga, S.; Oi, Y.; Kato, T.; An, D. K.; Okamoto, S.
Tetrahedron Lett. 2004, 45, 5585–5588. See also ref 6c: bidentate NHC and
dialkylzincs. (b) Larsen, A. O.; Leu, W.; Oberhuber, C. N.; Campbell, J. E.;
Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126, 11130–11131. (c) Van
Veldhuizen, J. J.; Campbell, J. E.; Giudici, R. E.; Hoveyda, A. H. J. Am.
Chem. Soc. 2005, 127, 6877–6882. Bidentate NHC and vinylaluminums; see
ref 9. Cu-catalyzed AAAr of vinylsilane substrates using bidentate NHC and
diarylzincs, see ref 7. Cu-free AAA using an NHC and alkyl Grignard
reagents: (d) Jackowski, O.; Alexakis, A. Angew. Chem., Int. Ed. 2010, 49,
3346–3350.
€
Backvall, J. E.; van Koten, G. Chem.;Eur. J. 1995, 1, 351–359.
J. Org. Chem. Vol. 76, No. 5, 2011 1399

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TABLE 1. Steric and Electronic Tuning of NHC-Cu 1 in AAAr with PhMgBra
entry
2
R
1
Ar
time (h)
3
yield (%)b,c
γ/Rd
ee (%)c
1
2
3
4
5
6
7
8
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2c
2c
2c
2d
2d
2d
C5H11
C5H11
C5H11
C5H11
C5H11
C5H11
C5H11
C5H11
C5H11
C5H11
C5H11
Pr
Pr
Pr
c-Hex
c-Hex
c-Hex
t-Bu
1a
1b
1c
1d
1e
1f
1g
1h
1i
Ph
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
6
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3aa
3ba
3ba
3ba
3ca
3ca
3ca
3da
3da
3da
98
67:33
92:8
89
76
72
63
4
2-MeC6H4
2,3-Me2C6H3
2,4-Me2C6H3
2,5-Me2C6H3
4-FC6H4
3-FC6H4
2-FC6H4
3,5-F2C6H3
4-CF3C6H4
4-MeC6H4
Ph
2-MeC6H4
4-FC6H4
Ph
2-MeC6H4
4-FC6H4
Ph
100
(89)
97
(93)
93
99
90
(100)
(100)
95
90:10
76:24
74:26
84:16
77:23
86:14
74:26
79:21
53:47
68:32
91:9
80:20
89:11
94:6
89:11
47:53
25:75
53:47
87
76
47
25
31
68
86
74
81
94
83
93
86
12
87
9
10
11
12
13
14
15
16
17
18
19
20
1j
1k
1a
1b
1f
1a
1b
1f
1a
1b
1f
100
98
96
97
(100)
97
(97)e
(99)e
61e
t-Bu
t-Bu
2-MeC6H4
4-FC6H4
17
3.5
aThe NHC-Cu complexes (X = Cl) were isolated and used in the reaction except for in entries 3-5, where the complexes (X = TC) were generated in
situ from CuTC, BF4 salts of the corresponding imidazolinium, and BuLi (see ref 13). Grignard reagents were added over 30 min in the reactions with 1.0
mmol of 2 (entries 1-14), and over 15 min in those with 0.5 mmol of 2 (entries 15-20). Conversion of 2 was 100%, unless otherwise mentioned. bThe
combined isolated yield of γ- and R-3 is presented, unless otherwise mentioned. cThe yields in parentheses and the enantioselectivity were determined by
GC. dThe γ/R ratios were determined by GC or 1H NMR of the crude material. eRemaining 2d was detected by GC in entries 18-20 (2%, 1%, and 22%,
respectively).
aryl groups in the copper(I)-catalyzed AAAr with Grignard
reagents (Figure 1). According to the previously described
methods,13 NHC-Cu complexes 1a, 1b, and 1f-k were
prepared and isolated, and complexes 1c-e were generated
in situ from the corresponding imidazolinium salt and copper(I)
thiophene-2-carboxylate (CuTC).
Steric Tuning of the NHC-Cu Complex in AAAr of Linear
Allylic Bromides. A 3 M diethyl ether solution of PhMgBr
(0.4 mL, 1.2 mmol) diluted with CH2Cl2 (0.5 mL) was added
over 30 min at -78 °C to a solution of NHC-CuCl catalyst
1a (2 mol %), with prototype benzhydryl groups on the
nitrogen atoms, and oct-2-enyl bromide (2a; 1.0 mmol) in
CH2Cl2 (2 mL). Allylic bromide 2a was completely con-
sumed within 30 min after the addition of the Grignard
reagent to give γ-3aa with 89% ee and moderate γ-selectivity
(γ/R 67:33; Table 1, entry 1).
Sterically tuned NHC-Cu complexes 1b-e were then
evaluated in the reaction. In the allylic arylation with catalyst
1b, having ortho-methyl substituents, γ-selectivity was dra-
matically improved (γ/R 92:8), but at the expense of enan-
tioselectivity (76% ee; entry 2). The introduction of a second
methyl group was then systematically examined at three posi-
tions, as shown in complexes 1c-e (entries 3-5). The use of
complexes 1c-e was not beneficial, however, and resulted in
the formation of γ-3aa with decreased enantioselectivity
(72%, 63%, and 4% ee) and less improved γ-selectivity (γ/
R 90:10, 76:24, and 74:26), respectively.17
AAAr of substrate 2b in the presence of catalyst 1a or 1b
gave similar results to those of 2a; γ-selectivity was 68:32
with 86% ee and 91:9 with 74% ee for 1a and 1b, respectively
(entries 12 and 13).13
Electronic Tuning of the NHC-Cu Complex in AAAr of
Linear Allylic Bromides. Next, electronically tuned NHC-
Cu complexes 1f-j were investigated in the reaction. When
complex 1f, having para-fluorophenyl groups, was used as a
catalyst, γ-3aa with 87% ee, comparable to entry 1, was
obtained with improved γ-selectivity (γ/R 84:16; entry 6).
Fluoro substitution at different positions was then exam-
ined. Catalysts 1g and 1h, having 3- and 2-fluorophenyl
groups, gave γ-3aa with decreased regio- and enantioselec-
tivity (γ/R 77:23, 76% ee; entry 7) and with lower enantio-
selectivity and comparable regioselectivity (47% ee, γ/R 86:14;
entry 8), respectively. 3,5-Difluoro-substituted NHC-Cu 1i
was also tested in the reactionof2a, but poor enantioselectivity
(25% ee) was observed with less effective improvement in
γ-selectivity (γ/R 74:26; entry 9).
(16) (a) Yamamoto, T.; Yamamoto, A.; Ikeda, S. J. Am. Chem. Soc. 1971,
93, 3350–3360. (b) Kurosawa, H.; Emoto, M.; Ohnishi, H.; Miki, K.;
Tatsumi, K.; Nakamura, A. J. Am. Chem. Soc. 1987, 109, 6333–6340.
(c) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G.; Principles
and Applications of Organotransition Metal Chemistry; University Science
Books: Mill Valley, CA, 1987.
(17) Evaluation of the NHCs using the in situ-generated NHC-CuTC
can be justified because the reaction with the in situ-generated CuTC
analogues of 1a and 1b gave almost the same results (97% yield, 88% ee,
γ/R 67:33 and 82% yield, 77% ee, γ/R 90:10, respectively) as those of 1a and
1b shown in Table 1, entries 1 and 2.
1400 J. Org. Chem. Vol. 76, No. 5, 2011

Selim et al.
JOCArticle
On the basis of these results, the best position of the
electron-withdrawing substituent should be the para-posi-
tion; therefore a more powerful electron-withdrawing group,
trifluoromethyl, was introduced on the phenyl groups. The
reaction using catalyst 1j, however, provided γ-3aa with
significantly lower enantioselectivity (31% ee), though the
γ/R ratio was improved to 79:21 (entry 10). The reaction
using catalyst 1k, having methyl groups at the para-position,
resulted in decreased regio- and enantioselectivity (γ/R
53:47, 68% ee; entry 11). Obviously, the electron-withdraw-
ing para-substituents increased the γ-selectivity, but the
bulkiness of the para-substituents seems to have decreased
enantioselectivity in this reaction.
TABLE 2. NHC-Cu-Catalyzed AAAr of 2a with Aryl Grignard
Reagentsa
entry
1
Ar
3
yield (%)b
γ/Rc
ee (%)d
1e
2e
3
4
5
6
7
8
9
1a
1f
1a
1f
1a
1f
1a
1f
1a
1f
1a
1f
Ph
Ph
3aa
3aa
3ab
3ab
3ac
3ac
3ad
3ad
3ae
3ae
3af
3af
98
93
98
92
99
99
98
99
96
96
96
96
67:33
84:16
64:36
82:18
67:33
79:21
87:13
83:17
82:18
88:12
84:16
79:21
89
87
88
84
85
79
80
56
86
66
82
52
4-MeC6H4
4-MeC6H4
4-MeOC6H4
4-MeOC6H4
4-ClC6H4
4-ClC6H4
4-FC6H4
4-FC6H4
3-FC6H4
3-FC6H4
The best catalyst, 1f, was applied to the reaction of 2b, and
γ-3ba was obtained with better γ-selectivity (γ/R 80:20) and
similar enantioselectivity (81% ee; entry 14).
10
11
12
AAAr of Branched Allylic Bromides. As a branched allylic
substrate, 3-cyclohexylprop-2-enyl bromide (2c) was exam-
ined. There was a dramatic increase in both the γ-selectivity
(γ/R 89:11) and enantioselectivity (94% ee), compared to
those in the reactions of 2a and 2b, when the reaction of 2c
was conducted in the presence of catalyst 1a (entry 15). This
result indicates that the increased steric repulsion between
the allylic substrate and the copper complex accelerated the
rate of reductive elimination of the initially formed γ-σ-allyl
complex II (Scheme 1). The reaction with sterically tuned 1b
gave γ-3ca with decreased enantioselectivity (83% ee) and
improved γ/R ratio (94:6; entry 16). Introduction of a
fluorine atom, an electron-withdrawing substituent, did
not affect the selectivity; the reaction with 1f afforded
γ-3ca with comparable regio- and enantioselectivity (γ/R
89:11, 93% ee; entry 17). These results suggested that steric
hindrance of γ-σ-allyl complex II derived from 1a and 2c was
sufficient to promote reductive elimination, and further
electronic tuning would be unnecessary.
aThe reactions were conducted with 0.5 mmol of 2a, and Grignard
reagents were added over 1 h except for entries 1 and 2, where 1.0 mmol
of 2a was used, and the addition time was 30 min. Conversion of 2a was
100%. bThe combined isolated yield of γ- and R-3a is presented. cThe γ/
R ratio was determined by 1H NMR of the crude material. dThe
enantioselectivity was determined by GC. eThe results in Table 1, entries
1 and 6, are shown again for comparison.
having an electron-donating methyl or methoxy group at the
para-positions improved the γ-selectivity with a similar level
of enantioselectivity (entries 4 and 6). Thus, using catalysts
1a and 1f, the reactions with 4-tolylmagnesium bromide
produced γ-3ab with 88% and 84% ee in a γ/R ratio of
64:36 and 82:18, respectively (entries 3 and 4), and those with
4-methoxyphenylmagnesium bromide produced γ-3ac with
85% and 79% ee in a γ/R ratio of 67:33 and 79:21, respec-
tively (entries 5 and 6).
In reactions using Grignard reagents with an electron-
deficient aryl group, good regio- and enantioselectivity were
realized by catalyst 1a, whereas electronically tuned catalyst
1f did not improve γ-selectivity, but decreased enantioselec-
tivity (entries 7-12). Thus, the reactions with a 4-chlorophe-
nyl Grignard reagent using 1a and 1f provided γ-3ad in 80%
and 56% ee with a γ/R ratio of 87:13 and 83:17, respectively
(entries 7 and 8). When a 4-florophenyl Grignard reagent
was utilized, γ-3ae with 86% and 66% ee were produced by
complexes 1a and 1f with a γ/R ratio of 82:18 and 88:12,
respectively (entries 9 and 10). A 3-fluorophenyl Grignard
reagent also showed the same tendency; the reactions with 1a
and 1f afforded γ-3af with 82% and 52% ee in a γ/R ratio of
84:16 and 79:21, respectively (entries 11 and 12). As illu-
strated in Scheme 1, these electron-deficient aryl species of
the Grignard reagents were incorporated into γ-σ-allyl inter-
mediate II; thus, these results also indicate that electron
deficiency of the γ-σ-allyl intermediate increased the forma-
tion of γ-products by promoting reductive elimination.
In short, the best catalyst for the reaction of 2a depended
on the Grignard reagents; 1a was the appropriate catalyst for
Grignard reagents with an electron-deficient aryl group, and
1f was more appropriate for the others.
The reactions of more sterically hindered allylic substrate
2d, having a tert-butyl group at the γ-position, were also
examined. In the presence of catalyst 1a, the reaction rate
was significantly slower, giving γ-3da with 86% ee without
regioselectivity (γ/R 47:53) along with a trace amount (2%)
of recovered 2d after 6 h (entry 18). The use of bulky catalyst
1b further increased the reaction time to 17 h, and γ-3da with
12% ee was obtained along with R-3da as a major isomer
(γ/R 25:75; entry 19). Electronic tuning of the catalyst
slightly improved the γ-preference (γ/R 53:47), and γ-3da
with 87% ee was obtained in 61% yield with 22% recovery of
2d (entry 20). Although the yield and regioselectivity were
unsatisfactory, good enantioselectivity was realized in the
reaction of the bulky allylic substrate. A possible explanation
for the observed low regioselectivity is as follows: (1) accu-
mulation of the aryl Grignard reagent, due to the slow
reaction, led to the formation of diarylcuprate species (X=
Ar, Scheme 1), which might facilitate isomerization to the
terminal σ-allyl complex IV through π-allyl complex III;5,15h
(2) an SN2 pathway leading directly to the terminal σ-allyl
complex IV was concomitant in the presence of severe steric
repulsion during the nucleophilic attack of complex I to the
γ-position of allylic substrate 2 (Scheme 1).
Electronic Effects of Aryl Grignard Reagents on AAAr of
Branched Allylic Bromide. The reaction of allylic bromide 2c
with various aryl Grignard reagents was examined (Table 3).
Similar to the reactions in entries 1 and 2, comparable results
were obtained in the reaction of a 4-tolyl Grignard reagent,
Electronic Effects of Aryl Grignard Reagents on AAAr of
Linear Allylic Bromide. The reaction of allylic bromide 2a
with various aryl Grignard reagents was examined (Table 2).
In the presence of 1f, Grignard reagents with an aryl group
J. Org. Chem. Vol. 76, No. 5, 2011 1401

Selim et al.
JOCArticle
TABLE 3. NHC-Cu-Catalyzed AAAr of 2c with Aryl Grignard
96% ee, 96% γ-product), and catalyst 1f, bearing N-(4,40-
difluorobenzhydryl) groups, for linear allylic substrates with
Grignard reagents having no electron-withdrawing group
(up to 87% ee, 84% γ-product). The results showed that
electron deficiency and moderate steric hindrance of the
complex derived from the catalysts, Grignard reagents, and
allylic substrates are important factors for achieving high
γ-selectivity and support the hypothesis that γ-selectivity is
governed by the relative rates of reductive elimination of the
γ-σ-allyl intermediate and isomerization to the R-σ-allyl
intermediate and the subsequent reductive elimination.
Reagentsa
Experimental Section
General Procedures. All reactions were carried out under
argon atmosphere in flame-dried glassware. Complexes 1a and
1b were prepared according to the reported procedure.13 CuCl
was purchased and used as received. CuTC was prepared
according to the reported procedure.18 Grignard reagents were
purchased from Aldrich. A 3 M solution of PhMgBr in Et2O was
used as received. Solutions of 4-FC6H4MgBr (2 M),
4-ClC6H4MgBr (1 M), and 4-CH3C6H4MgBr (0.5 M) in Et2O
were concentrated to ca. 3 M in vacuo prior to use. Solutions of
3-FC6H4MgBr (1 M), 4-MeOC6H4MgBr (0.5 M), and 3,4-
Cl2C6H3MgBr (0.5 M) in THF, and 3,4-(methylenedioxy)-
phenylMgBr (1 M) in toluene/THF (1:1), were used after
replacing most of the solvents with toluene by two consecutive
additions of toluene followed by vacuum removal of the solvent
to give a final concentration of approximately 3 M. CH2Cl2 was
distilled from CaH2 and stored with MS 4A under argon.
Substrates 2a,19 2b,19 2c20 and 2d20 were prepared according
to the literature procedures. Column chromatography was
performed using silica gel. TLC was performed using precoated
silica gel plates (0.25 mm thick, 60 F254), and the products were
observed under UV light and with either phosphomolybdic acid
or KMnO4 reagents.
The wave numbers of maximum absorption peaks of IR
spectroscopy are presented in cm-1. 1H and 13C NMR spectra
were recorded in CDCl3 at 500 and 125 MHz, respectively,
unless otherwise mentioned. Chemical shifts and coupling con-
stants are presented in ppm δ relative to tetramethylsilane and
Hz, respectively. Data are reported as follows: chemical shift,
integration, multiplicity (s=singlet, d=doublet, t=triplet, q=
quartet, br = broad, and m = multiplet), coupling constants,
assignment. 13C peak multiplicity assignments were made on the
basis of DEPT data. The 1H and 13C NMR data are reported for
γ-products. Specific rotation was measured in a 10 cm cell. For
the AAAr products, the specific rotation and c of the R,γ-
mixture were reported. The enantioselectivity of chiral products
was determined by comparison of the chiral stationary phase
GC or HPLC traces with those of the corresponding racemic
products. The absolute configurations of the products other
than γ-3aa and γ-3ca were tentatively assigned by analogy.
Preparation of Chiral NHC-Cu Complexes. Synthesis of
Chiral Imidazolinium Salts. Typical Procedure for the Synthesis
of N,N0-Dibenzohydryldiamines. (1S,2S)-N,N0-Bis(bis(2,3-di-
methylphenyl)methyl)-1,2-diphenylethane-1,2-diamine (C). A mix-
ture of (1S,2S)-1,2-diphenylethane-1,2-diamine (1.14 g, 5.4
mmol), bis(2,3-dimethylphenyl)methyl bromide (3.60 g, 11.9
mmol), and Na2CO3 (2.29 g, 21.6 mmol) in DMPU (16 mL)
was stirred at 120 °C. After 2 h, water (60 mL) was added, and the
aThe reactions were conducted with 0.5 mmol of 2c, and Grignard
reagents were added over 15 min, except for entries 7 and 8, where
Grignard reagents were added over 1 h. Conversion of 2a was 100%,
unless otherwise mentioned. bThe combined isolated yield of γ- and R-3a
is presented. cThe γ/R ratio was determined by GC or 1H NMR of the
crude material. dThe enantioselectivity was determined by GC, unless
otherwise mentioned. eThe results in Table 1, entries 15 and 17, are
shown again for comparison. fThe Grignard reagent was added over 1 h.
gRemaining 2c was detected by GC in entries 7 and 8 (16% and 40%,
respectively). hThe enantioselectivity was determined by HPLC after
conversion to alcohol.
and regardless of whether 1a or 1f was used as a catalyst, 3cb
with high enantiopurity (96% and 94% ee) was obtained in
good γ-selectivity (γ/R 87:13 and 84:16), respectively (entries
3 and 4). Therefore, the following reactions were conducted
using catalyst 1a.
As expected, Grignard reagents bearing electron-with-
drawing 4-chloro and 4-fluoro substituents underwent
AAAr in a highly γ-selective manner, and 3cd and 3ce were
obtained in 93% and 92% ee with a γ/R ratio of 96:4 and
95:5, respectively (entries 5 and 6). When a 3,4-dichlorophe-
nyl Grignard reagent was used, 3cg with 86% ee was
obtained also with high γ-selectivity (96:4) along with 16%
of recovered 2c (entry 7). With a benzodioxolanyl Grignard
reagent, the reaction was also slow without complete con-
version of 2c, but 3ch was obtained with high enantioselec-
tivity (93% ee) and a high γ/R ratio (91:9) in moderate yield
(41%; entry 8).
These results clearly indicate that the electron deficiency
of the γ-σ-allyl intermediate also promotes the formation of
γ-products in the reaction of 2c.
Conclusions
We performed steric and electronic tuning of chiral NHC
and developed chiral NHC-Cu(I)-catalyzed γ-selective
AAAr of aliphatic allylic bromides with aryl Grignard
reagents. The suitable catalyst depended on the allylic sub-
strates as well as the Grignard reagents; catalyst 1a, bearing
N-benzhydryl groups, afforded good results for linear allylic
substrates with Grignard reagents having an electron-defi-
cient aryl group (up to 86% ee, 88% γ-product) and for
branched allylic substrates with any Grignard reagents (up to
(18) Allred, G. D.; Liebeskind, L. S. J. Am. Chem. Soc. 1996, 118, 2748–
2749.
(19) Tallman, K. A.; Roschek, B., Jr.; Porter, N. A. J. Am. Chem. Soc.
2004, 126, 9240–9247.
(20) Tallman, K. A.; Rector, C. L.; Porter, N. A. J. Am. Chem. Soc. 2009,
131, 5635–5641.
1402 J. Org. Chem. Vol. 76, No. 5, 2011

Selim et al.
JOCArticle
whole was extracted with EtOAc (3 ꢀ 30 mL). The combined
organic layers were washed with water (2 ꢀ 30 mL) and brine
(2 ꢀ 30 mL), dried over Na2SO4, and then concentrated in vacuo.
The resulting crude mixture was purified by column chromato-
graphy (hexane/EtOAc = 15:1) to afford the title compound
(68%) as a colorless, amorphous solid of mp 83-86 °C: [R]25D -73.7
(c 1.00, CHCl3). IR (KBr): 3336, 2918, 1585, 1458, 1094, 725, 700.
1H NMR: 1.71 (6H, s), 1.87 (6H, s), 2.20 (6H, s), 2.23 (6H, s), 2.51
(2H, s), 3.78 (2H, s), 4.96 (2H, s), 6.91-7.00 (10H, m), 7.02-7.09
(10H, m), 7.56-7.59 (2H, m). 13C NMR: 14.4 (CH3), 14.5 (CH3),
20.7 (CH3), 20.9 (CH3), 56.2 (CH), 65.9 (CH), 125.2 (CH), 125.3
(CH), 125.8 (CH), 126.4 (CH), 126.9 (CH), 127.7 (CH), 128.1
(CH), 128.3 (CH), 128.7 (CH), 134.7 (C), 134.9 (C), 136.56 (C),
136.58 (C), 140.5 (C), 141.6 (C), 141.7 (C). EIMS: m/z 328 (M/2).
162.9 (d, J=246, C), 163.2 (d, J=246, C). EIMS m/z: 308 (M/2).
Anal. Calcd for C40H32F4N2: C, 77.90; H, 5.23; N, 4.54. Found: C,
77.84; H, 5.27; N, 4.54.
(1S,2S)-N,N0-Bis(bis(2-fluorophenyl)methyl)-1,2-diphenylethane-
1,2-diamine (H). Column chromatography (hexane/EtOAc=14:1)
gave the title compound (74%) as a pale yellow, amorphous solid of
mp 131-132 °C: [R]25 þ52.3 (c 1.01, CHCl3). IR (KBr): 3433,
D
3071, 3040, 1583, 1489, 1458, 1227, 756. 1H NMR: 2.86 (2H, br s),
3.67 (2H, s), 5.13 (2H, s), 6.89-6.95 (4H, m), 7.00-7.05 (6H, m),
7.08-7.10 (2H, m), 7.14-7.21 (12H, m), 7.44-7.47 (2H, m). 13
C
NMR: 51.5 (CH), 66.2 (CH), 115.4 (d, J=22, CH), 115.5 (d, J=22,
CH), 124.03 (d, J = 9, CH), 124.05 (d, J = 9, CH), 127.1 (CH),
128.01 (CH), 128.04 (CH), 128.49 (d, J=9, CH), 128.54 (d, J=3,
CH), 128.57 (d, J=9, CH), 129.07 (d, J=3, CH), 129.12 (d, J=13,
C), 130.4 (d, J=13, C), 140.5 (C), 160.2 (d, J=247, C), 161.0 (d, J=
247, C). FABMS m/z: 617 (M þ Hþ), 308 (M/2). Anal. Calcd for
C40H32F4N2: C, 77.90; H, 5.23; N, 4.54. Found: C, 77.64; H, 5.10;
N, 4.62.
Anal. Calcd for C48H52N2 0.5H2O: C, 86.57; H, 8.02; N, 4.21.
3
Found: C, 86.51; H, 8.02; N, 4.09.
(1S,2S)-N,N0-Bis(bis(2,4-dimethylphenyl)methyl)-1,2-diphenyl-
ethane-1,2-diamine (D). Column chromatography (hexane/
EtOAc = 15:1) gave the title compound (54%) as a colorless,
amorphous solid of mp 87-90 °C: [R]25D -45.0 (c 0.97, CHCl3).
IR (KBr): 3328, 2918, 1612, 1499, 1454, 804, 700. 1H NMR: 1.78
(6H, s), 1.96 (6H, s), 2.26 (6H, s), 2.31 (6H, s), 2.48 (2H, s), 3.75
(2H, s), 4.76 (2H, s), 6.84 (2H, s), 6.86-6.90 (4H, m), 6.91-6.94
(4H, m), 6.96-7.02 (4H, m), 7.06-7.08 (6H, m), 7.56 (1H, s),
7.58 (1H, s). 13C NMR: 18.9 (CH3), 19.0 (CH3), 20.8 (CH3), 20.9
(CH3), 55.3 (CH), 65.8 (CH), 126.5 (CH), 126.7 (CH), 126.8
(CH), 127.6 (CH), 127.7 (CH), 128.3 (CH), 128.6 (CH), 131.1
(CH), 131.3 (CH), 135.6 (C), 136.01 (C), 136.03 (C), 136.2 (C),
137.3 (C), 138.8 (C), 141.6 (C). EIMS m/z: 328 (M/2). Anal.
Calcd for C48H52N2: C, 87.76; H, 7.98; N, 4.26. Found: C, 87.70;
H, 8.05; N, 4.13.
(1S,2S)-N,N0-Bis(bis(3,5-difluorophenyl)methyl)-1,2-diphenyl-
ethane-1,2-diamine (I). Column chromatography (hexane/
EtOAc=20:1) gave the title compound (71%) as an off-white,
amorphous solid of mp 64-66 °C: [R]21 þ33.9 (c 1.24,
D
CHCl3). IR (KBr): 3317, 3094, 2855, 1605, 1458, 1319, 1119,
988, 856, 764, 702. H NMR: 2.47 (2H, s), 3.63 (2H, s), 4.45
1
(2H, s), 6.53-6.57 (4H, m), 6.64-6.77 (8H, m), 7.02-7.04
(4H, m), 7.24-7.26 (6H, m). 13C NMR: 62.4 (CH), 65.7 (CH),
102.9 (t, J=25, CH), 103.2 (t, J=25, CH), 110.0 (dd, J=6.2,
20, CH), 110.3 (dd, J=6.2, 20, CH), 127.6 (CH), 127.9 (CH),
128.6 (CH), 139.5 (C), 146.2 (t, J=8.3, C), 147.0 (t, J=8.3, C),
163.1 (dd, J=12.4, 249, C), 163.3 (dd, J=12.4, 250, C). EIMS
m/z: 344 (M/2). Anal. Calcd for C40H28F8N2: C, 69.76; H,
4.10; N, 4.07. Found: C, 69.82; H, 4.16; N, 3.98.
(1S,2S)-N,N0-Bis(bis(2,5-dimethylphenyl)methyl)-1,2-diphenyl-
ethane-1,2-diamine (E). Column chromatography (hexane/
EtOAc = 15:1) gave the title compound (57%) as a colorless,
amorphous solid of mp 80-82 °C: [R]25D -96.6 (c 1.00, CHCl3).
IR (KBr): 3326, 2920, 1498, 1454, 808, 700. 1H NMR: 1.82 (6H,
s), 1.88 (6H, s), 2.21 (6H, s), 2.22 (6H, s), 2.49 (2H, s), 3.72 (2H,
s), 4.81 (2H, s), 6.87-6.97 (14H, m), 7.06-7.11 (6H, m), 7.59
(2H, s). 13C NMR: 18.4 (CH3), 18.8 (CH3), 21.2 (CH3), 55.7
(CH), 65.9 (CH), 126.9 (CH), 127.0 (CH), 127.4 (CH), 127.8
(CH), 128.4 (CH), 128.6 (CH), 129.0 (CH), 130.2 (CH), 130.3
(CH), 133.0 (C), 133.3 (C), 135.07 (C), 135.09 (C), 140.2 (C),
141.3 (C), 141.9 (C). CIMS m/z: 657 (M þ Hþ). HRMS-CI m/z:
[M þ H]þ calcd for C48H53N2 657.4209, found 657.4203.
(1S,2S)-N,N0-Bis(bis(4-fluorophenyl)methyl)-1,2-diphenylethane-
1,2-diamine (F). Column chromatography (hexane/EtOAc=10:1)
gave the title compound (75%) as a white, amorphous solid of mp
162-164 °C: [R]21D þ35.8 (c 0.65, CHCl3). IR (KBr): 3317, 3032,
2839, 1605, 1504, 1450, 1227, 1157, 1095, 833, 702. 1H NMR: 2.49
(2H, s), 3.59 (2H, s), 4.49 (2H, s), 6.90-6.95 (8H, m), 6.99-7.02
(8H, m), 7.17-7.20 (10H, m). 13C NMR: 62.1 (CH), 65.7 (CH),
115.2 (d, J= 22, CH), 115.4 (d, J = 22, CH), 127.2 (CH), 127.9
(CH), 128.2 (CH), 128.7 (d, J=8.3, CH), 129.1 (d, J=8.3, CH),
137.6 (d, J=4.1, C), 140.3 (d, J=3.1, C), 140.7 (C), 161.8 (d, J=
246, C), 161.9 (d, J=245, C). EIMS m/z: 308 (M/2). Anal. Calcd for
C40H32F4N2: C, 77.90; H, 5.23; N, 4.54. Found: C, 78.17; H, 5.36;
N, 4.60.
(1S,2S)-N,N0-Bis(bis(3-fluorophenyl)methyl)-1,2-diphenylethane-
1,2-diamine (G). Column chromatography (hexane/EtOAc =
1:0-40:1-10:1) gave the title compound (81%) as an off-white,
amorphous solid of mp 52-54 °C: [R]21D þ36.7 (c 1.54, CHCl3). IR
(KBr): 3310, 3032, 2847, 1589, 1481, 1450, 1242, 1134, 1072, 880,
772, 694. 1H NMR: 2.60 (2H, s), 3.62 (2H, s), 4.51 (2H, s),
6.83-7.01 (16H, m), 7.17-7.27 (10H, m). 13C NMR: 62.6 (CH),
65.8 (CH), 114.0 (d, J=21, CH), 114.1 (d, J=23, CH), 114.3 (d, J=
22, CH), 114.5 (d, J=22, CH), 122.7 (d, J=3, CH), 123.3 (d, J=2,
CH), 127.4 (CH), 127.9 (CH), 128.2 (CH), 129.9 (d, J=8, CH),
130.2 (d, J=8, CH), 140.3 (C), 145.5 (d, J=6, C), 146.6 (d, J=6, C),
(1S,2S)-N,N0-Bis(bis(4-trifluoromethylphenyl)methyl)-1,2-di-
phenylethane-1,2-diamine (J). Column chromatography (hexane/
EtOAc= 1:0-20:1) gave the title compound (80%) as a white,
amorphous solid of mp 95-97 °C: [R]25D þ34.5 (c 0.54, CHCl3).
IR(KBr): 3317, 3062, 1620, 1458, 1327, 1172, 1126, 1065, 826, 702.
1H NMR: 2.55 (2H, s), 3.64 (2H, s), 4.64 (2H, s), 7.04-7.06 (4H,
m), 7.12 (4H, d, J=8.3), 7.24-7.26 (6H, m), 7.33 (4H, d, J=8.3),
7.48 (4H, d, J=8.3), 7.53 (4H, d, J=8.3). 13C NMR: 62.9 (CH),
65.8 (CH), 124.06 (q, J=272, CF3), 124.11 (q, J=272, CF3), 125.6
(q, J=4, CH), 125.7 (q, J=4, CH), 127.5 (CH), 127.7 (CH), 127.8
(CH), 127.9 (CH), 128.5 (CH), 129.7 (q, J=32, C), 129.8 (q, J=
33, C), 140.0 (C), 146.3 (C), 147.4 (C). EIMS m/z: 408 (M/2).
HRMS-FAB m/z: [M þ H]þ calcd for C44H33F12N2 817.2452,
found 817.2432.
(1S,2S)-N,N0-Bis(di-p-tolylmethyl)-1,2-diphenylethane-1,2-
diamine (K). Column chromatography (hexane/CHCl3
=
1:0-1:2) gave the title compound (56%) as a white, amor-
phous solid of mp 65-67 °C: [R]25D þ39.6 (c 1.08, CHCl3). IR
(KBr): 3310, 3024, 2924, 2862, 1512, 1450. 1H NMR: 2.29
(6H, s), 2.32 (6H, s), 2.68 (2H, s), 3.63 (2H, s), 4.46 (2H, s),
6.95-6.96 (4H, m), 7.06 (8H, m), 7.07 (4H, m), 7.11-7.12 (6H,
m), 7.18 (4H, d, J=8.0). 13C NMR: 21.0 (CH3), 21.1 (CH3),
62.6 (CH), 65.8 (CH), 126.7 (CH), 127.0 (CH), 127.5 (CH),
127.8 (CH), 128.1 (CH), 128.9 (CH), 129.1 (CH), 136.18 (C),
136.21 (C), 140.5 (C), 141.2 (C), 142.3 (C). EIMS m/z: 300 (M/
2), 195. Anal. Calcd for C44H44N2: C, 87.96; H, 7.38; N, 4.66.
Found: C, 87.77; H, 7.31; N, 4.56.
Typical Procedure for the Synthesis of Imidazolinium Salts.
(4S,5S)-1,3-Bis(bis(2,3-dimethylphenyl)methyl)-4,5-diphenylimi-
dazolinium Tetrafluoroborate (C1). A suspension of C (2.17 g,
3.31 mmol) and NH4BF4 (0.38g, 3.65 mmol) inCH(OEt)3 (20mL)
was stirred at 120 °C for 2 h. The mixture was cooled to rt,
filtrated, and concentrated in vacuo. After azeotropic evapora-
tion with toluene (3 ꢀ 10 mL), the resulting residue was purified
by column chromatography (hexane/EtOAc=1:1) to afford the
title compound (76%) as a colorless, amorphous solid of mp
J. Org. Chem. Vol. 76, No. 5, 2011 1403

Selim et al.
JOCArticle
134-136 °C: [R]25D -383 (c 1.01, CHCl3). IR (KBr): 2918, 1630,
1458, 1035, 729. 1H NMR: 1.71 (6H, s), 2.08 (6H, s), 2.20 (6H, s),
2.24 (6H, s), 5.34 (2H, s), 5.92 (2H, s), 6.70-6.72 (2H, m), 6.76
(1H, s), 6.91-6.94 (2H, m), 7.03-7.05 (2H, m), 7.16-7.21 (8H,
m), 7.40-7.44 (8H, m). 13C NMR: 14.2 (CH3), 14.5 (CH3), 20.56
(CH3), 20.63 (CH3), 58.9 (CH), 73.2 (CH), 124.6 (CH), 126.2
(CH), 126.4 (CH), 126.5 (CH), 128.5 (CH), 129.9 (CH), 130.9
(CH), 131.3 (CH), 131.8 (C), 132.2 (C), 132.5 (C), 135.0 (C),
135.1 (C), 138.6 (C), 138.7 (C), 154.6 (CH). FABMS m/z: 668
J=7, C), 136.8 (d, J=6, C), 157.4 (CH), 162.9 (d, J=249, C),
163.1 (d, J=249, C). FABMS m/z: 627 (M - BF4). Anal. Calcd
for C41H31BF8N2: C, 68.92; H, 4.37; N, 3.92. Found: C, 69.06;
H, 4.36; N, 3.96.
(4S,5S)-1,3-Bis(bis(2-fluorophenyl)methyl)-4,5-diphenylimi-
dazolinium Tetrafluoroborate (H1). Column chromatography
(CHCl3/EtOH=1:0-9:1) gave the title compound (86%) as a
yellow, amorphous solid of mp 85-88 °C: [R]25D -199.2 (c 1.02,
CHCl3). IR (KBr): 1636, 1489, 1219, 1057. 1H NMR: 5.11 (2H,
s), 6.08 (2H, s), 6.96-7.00 (2H, m), 7.07-7.11 (2H, m),
7.13-7.16 (2H, m), 7.20-7.21 (4H, m), 7.28-7.32 (6H, m),
7.37-7.42 (8H, m), 7.47-7.51 (3H, m). 13C NMR: 55.1 (CH),
74.9 (CH), 115.7 (d, J=21, CH), 116.3 (d, J=21, CH), 120.3 (d,
J=11, C), 120.5 (d, J=12, C), 125.6 (d, J=3, CH), 125.8 (d, J=
3, CH), 127.9 (CH), 129.8 (CH), 130.6 (CH), 130.6 (CH), 131.1
(CH), 132.0 (d, J=7, CH), 133.1 (C), 155.8 (CH), 159.9 (d, J=
249, C), 160.3 (d, J = 249, C). FABMS m/z: 627 (M - BF4).
Anal. Calcd for C41H31BF8N2: C, 68.92; H, 4.37; N, 3.92.
Found: C, 68.62; H, 4.46; N, 3.99.
(M þ H - BF4). Anal. Calcd for C49H51BF4N2 0.3H2O: C,
3
77.42; H, 6.84; N, 3.69. Found: C, 77.25; H, 6.89; N, 3.69.
(4S,5S)-1,3-Bis(bis(2,4-dimethylphenyl)methyl)-4,5-diphenyli-
midazolinium Tetrafluoroborate (D1). Column chromatography
(CHCl3/EtOH=1:0-9:1) gave the title compound (68%) as a
pale yellow, amorphous solid of mp 132-135 °C: [R]25D -382 (c
1.08, CHCl3). IR (KBr): 2922, 1631, 1499, 1055, 758. 1H NMR:
1.69 (6H, s), 2.21 (6H, s), 2.23 (6H, s), 2.36 (6H, s), 5.29 (2H, s),
5.63 (2H, s), 6.62 (1H, s), 6.71-6.73 (2H, m), 6.79-6.81 (2H, m),
6.94 (2H, s), 7.01 (2H, s), 7.19-7.21 (4H, m), 7.23-7.25 (2H, m),
7.40-7.41 (2H, m), 7.46-7.48 (6H, m). 13C NMR: 18.4 (CH3),
18.6 (CH3), 20.7 (CH3), 20.9 (CH3), 57.6 (CH), 72.9 (CH), 126.2
(CH), 127.6 (CH), 127.8 (CH), 128.3 (C), 128.4 (CH), 128.6 (C),
128.8 (CH), 130.0 (CH), 131.0 (CH), 132.37 (C), 132.44 (CH),
132.8 (CH), 136.0 (C), 136.5 (C), 139.2 (C). 139.9 (C), 153.7
(CH). FABMS m/z: 668 (M þ H - BF4). Anal. Calcd for
(4S,5S)-1,3-Bis(bis(3,5-difluorophenyl)methyl)-4,5-diphenyli-
midazolinium Tetrafluoroborate (I1). Recrystallization from
CH2Cl2/Et2O gave the title compound (77%) as a white powder
of mp 258-260 °C: [R]21 -175.9 (c 0.51, CHCl3). IR (KBr):
D
1
3094, 1620, 1458, 1327, 1211, 1126, 1065, 856, 718. H NMR:
5.04 (2H, s), 6.04 (2H, s), 6.74-6.83 (12H, m), 7.14-7.16 (4H,
m), 7.44-7.45 (6H, m), 8.19 (1H, s). 13C NMR (CD2Cl2): 64.7
(CH), 75.0 (CH), 105.7 (t, J=25, CH), 105.8 (t, J=25, CH),
112.2. (dd, J=7.2, 21, CH), 112.6 (dd, J=7.2, 21, CH), 128.0
(CH), 130.5 (CH), 131.1 (CH), 134.1 (C), 137.7 (t, J=9.3, C),
138.2 (t, J =9.3, C), 158.7 (CH), 163.8 (dd, J=12.4, 252, C),
164.0 (dd, J=12.4, 252, C). FABMS m/z: 699 (M - BF4). Anal.
C49H51BF4N2 0.5H2O: C, 77.06; H, 6.86; N, 3.67. Found: C,
3
76.98; H, 6.69; N, 3.93.
(4S,5S)-1,3-Bis(bis(2,5-dimethylphenyl)methyl)-4,5-diphenyli-
midazolinium Tetrafluoroborate (E1). Recrystallization from
EtOH gave the title compound (60%) as colorless needles of
mp 255-257 °C: [R]25D -442 (c 1.04, CHCl3). IR (KBr): 2922,
1627, 1504, 1055, 758. 1H NMR: 1.78 (6H, s), 2.14-2.15 (12H,
m), 2.54 (6H, s), 5.22 (2H, s), 5.76 (2H, s), 6.71 (2H, s), 6.89 (1H,
s), 6.97-7.01 (4H, m), 7.08-7.12 (4H, m), 7.20-7.24 (6H, m),
7.45-7.49 (6H, m). 13C NMR: 18.1 (CH3), 18.2 (CH3), 20.8
(CH3), 21.3 (CH3), 58.1 (CH), 73.0 (CH), 127.0 (CH), 128.2
(CH), 129.1 (CH), 129.9 (CH), 130.0 (CH), 130.4 (CH), 131.0
(CH), 131.5 (C), 131.6 (C), 131.7 (CH), 132.0 (CH), 133.4 (C),
136.6 (C), 136.9 (C), 154.8 (CH). FABMS m/z: 668 (M þ H -
BF4). Anal. Calcd for C49H51BF4N2: C, 77.98; H, 6.81; N, 3.71.
Found: C, 78.01; H, 6.78; N, 3.51.
Calcd for C41H27BF12N2 0.5H2O: C, 61.90; H, 3.55; N, 3.52.
3
Found: C, 61.77; H, 3.39; N, 3.90.
(4S,5S)-1,3-Bis(bis(4-trifluoromethylphenyl)methyl)-4,5-di-
phenylimidazolinium Tetrafluoroborate (J1). Column chroma-
tography (CHCl3/EtOH=15:1) gave the title compound (83%)
as a white solid of mp 238-240 °C: [R]21D -238.6 (c 0.56, benzene).
IR (KBr): 3071, 2368, 1628, 1420, 1327, 1173, 1126, 1072, 826, 702.
1H NMR (CD2Cl2): 5.14 (2H, s), 5.96 (2H, s), 7.19 (4H, m),
7.44-7.47 (14H, m), 7.59-7.67 (9H, m). 13C NMR (CD2Cl2):
65.3 (CH), 75.0 (CH), 124.0 (q, J=273, CF3), 124.1 (q, J=272,
CF3), 127.05 (q, J= 3, CH), 127.13 (q, J= 3, CH), 128.1 (CH),
129.3 (CH), 130.0 (CH), 130.6 (CH), 131.1 (CH), 132.0 (q,
J= 32, C), 132.2 (q, J= 34, C), 134.0 (C), 137.9 (C), 138.6 (C),
157.6 (CH). FABMS m/z: 827 (M - BF4). Anal. Calcd for C45H31-
BF16N2: C, 59.10; H, 3.42; N, 3.06. Found: C, 59.08; H, 3.52;
N, 3.17.
(4S,5S)-1,3-Bis(bis(4-fluorophenyl)methyl)-4,5-diphenylimi-
dazolinium Tetrafluoroborate (F1). Column chromatography
(CHCl3/EtOH = 10:1) gave a white, amorphous solid, which
was recrystallized from CHCl3/Et2O to give the title compound
(77%) as colorless needles of mp 115-117 °C: [R]21 -290.3
D
(c 0.71, CHCl3). IR (KBr): 3078, 1628, 1512, 1234, 1165, 1057,
833. 1H NMR: 4.97 (2H, s), 5.73 (2H, s), 7.02 (4H, dd, J=8.6,
8.6), 7.07 (4H, dd, J=8.6, 8.6), 7.12-7.14 (4H, m), 7.23-7.29
(8H, m), 7.43-7.45 (6H, m), 7.54 (1H, s). 13C NMR: 64.5 (CH),
74.4 (CH), 116.6 (d, J=22, CH), 116.7 (d, J=22, CH), 127.7
(CH), 129.9 (d, J=3, C), 130.06 (d, J=8, CH), 130.11 (CH),
130.4 (CH), 130.5 (d, J=3, C), 131.1 (d, J=8, CH), 134.0 (C),
156.4 (CH), 163.0 (d, J=249, C), 163.1 (d, J=250, C). FABMS
m/z: 627 (M - BF4). Anal. Calcd for C41H31BF8N2: C, 68.92; H,
4.37; N, 3.92. Found: C, 68.63; H, 4.34; N, 3.96.
(4S,5S)-1,3-Bis(di-p-tolylmethyl)-4,5-diphenylimidazolinium Tet-
rafluoroborate (K1). Column chromatography (CHCl3/EtOH =
1:0-9:1) gave the title compound (99%) as a pale yellow, amor-
phous solid of mp 101-103 °C: [R]25D -279.0 (c 1.03, CHCl3). IR
(KBr): 3032, 2924, 1628, 1211, 1057. 1H NMR: 2.27 (6H, s), 2.33
(6H, s), 4.99 (2H, s), 5.53 (2H, s), 7.08 (3H, m), 7.10 (8H, m),
7.15-7.17 (4H, m), 7.21-7.23 (4H, m), 7.25-7.27 (2H, m),
7.42-7.47 (6H, m). 13C NMR: 21.0 (CH3), 21.1 (CH3), 65.0
(CH), 73.9 (CH), 127.6 (CH), 127.7 (CH), 128.7 (CH), 130.0
(CH), 130.1 (CH), 130.2 (CH), 130.9 (C), 131.9 (C), 134.2 (C),
139.1 (C), 139.4 (C), 155.5 (CH). FABMS m/z: 611 (M - BF4).
HRMS-FAB m/z: [M - BF4]þ calcd for C45H43N2, 611.3421;
(4S,5S)-1,3-Bis(bis(3-fluorophenyl)methyl)-4,5-diphenylimi-
dazolinium Tetrafluoroborate (G1). Column chromatography
(CHCl3/EtOH=30:1) gave a white solid, which was recrystal-
lized from CH2Cl2/Et2O to give the title compound (83%) as
found, 611.3417. Anal. Calcd for C45H43BF4N2 0.05CHCl3: C,
3
colorless needles of mp 184-185 °C: [R]21 -247.0 (c 0.6,
76.79; H, 6.16; N, 3.98. Found: C, 76.54; H, 6.34; N, 4.08.
D
Preparation of NHC-Cu Complexes 1f-k. Typical Proce-
dure. [(4S,5S)-1,3-Bis(bis(4-fluorophenyl)methyl)-4,5-diphenyli-
midazolidin-2-ylidene]copper(I) Chloride (1f). A mixture of F1
(140 mg, 0.20 mmol), NaOtBu (21 mg, 0.22 mmol), and CuCl
(20 mg, 0.20 mmol) in THF (3 mL) was stirred at rt for 3 h.
The mixture was filtrated through Celite and concentrated
in vacuo to give a crude mixture, which was purified by column
CHCl3). IR (KBr): 3071, 1620, 1489, 1450, 1250, 1211, 1065,
1
756. H NMR: 5.06 (2H, s), 5.86 (2H, s), 6.79-6.84 (4H, m),
6.97-7.05 (4H, m), 7.15-7.22 (8H, m), 7.36-7.44 (10H, m),
7.72 (1H, s). 13C NMR: 64.8 (CH), 74.5 (CH), 115.3 (d, J=22,
CH), 115.7 (d, J=23, CH), 116.5 (d, J=21, CH), 116.7 (d, J=
21, CH), 124.0 (d, J=3, CH), 125.1 (d, J=3, CH), 127.7 (CH),
130.1 (CH), 130.4 (CH), 131.6 (d, J=7, CH), 134.0 (C), 136.4 (d,
1404 J. Org. Chem. Vol. 76, No. 5, 2011

Selim et al.
JOCArticle
chromatography (benzene to CHCl3/EtOH=20:1) to afford the
title compound as an off-white, amorphous solid (117 mg, 81%)
(2H, s), 7.05-7.07 (4H, m), 7.14 (4H, d, J = 8.2), 7.40-7.43
(6H, m), 7.45 (4H, d, J=8.2), 7.59 (4H, d, J=8.2), 7.75 (4H, d,
J=8.2). 13C NMR: 64.5 (CH), 74.8 (CH), 123.74 (q, J=271,
CF3), 123.75 (q, J=273, CF3), 126.5 (q, J=4, CH), 126.7 (q,
J=3, CH), 127.3 (CH), 128.9 (CH), 129.1 (CH), 129.9 (CH),
130.0 (CH), 131.4 (q, J=32, C), 131.5 (q, J=33, C), 136.8 (C),
of mp 205-207 °C (dec): [R]25 -246.5 (c 0.5, CHCl3). IR
D
(KBr): 3060, 1605, 1504, 1458, 1227, 1157, 833. 1H NMR: 4.52
(2H, s), 5.39 (2H, s), 6.97-7.05 (12H, m), 7.14-7.17 (4H, m),
7.29-7.32 (4H, m), 7.40-7.41 (6H, m). 13C NMR: 63.8 (CH),
74.6 (CH), 116.3 (d, J=22, CH), 116.5 (d, J=22, CH), 127.4
(CH), 129.6 (CH), 129.7 (CH), 130.1 (d, J=8, CH), 130.4 (d, J=
8, CH), 132.4 (d, J=3, C), 133.7 (d, J=3, C), 137.5 (C), 162.8 (d,
J=248, C), 163.0 (d, J=248, C), 198.6 (C). FABMS m/z: 689
140.0 (C), 141.0 (C), 199.5 (C). Anal. Calcd for C45H30
-
ClCuF12N2: C, 58.39; H, 3.27; N, 3.03. Found: C, 58.16; H,
3.25; N, 3.09.
[(4S,5S)-1,3-Bis(di-p-tolylmethyl)-4,5-diphenylimidazolidin-2-
ylidene]copper(I) Chloride (1k). Column chromatography
(benzene to CHCl3/EtOH = 19:1) gave the title compound
as a colorless, amorphous solid (199 mg, 93%) of mp 102-
(M - Cl). Anal. Calcd for C41H30ClCuF4N2 H2O: C, 66.21; H,
3
4.34; N, 3.77. Found: C, 66.08; H, 4.29; N, 3.79.
[(4S,5S)-1,3-Bis(bis(3-fluorophenyl)methyl)-4,5-diphenylimi-
dazolidin-2-ylidene]copper(I) Chloride (1g). Column chromatog-
raphy (benzene to CHCl3/EtOH=50:1) gave the title compound
as an off-white, amorphous solid (209 mg, 96%) of mp 219-
106 °C: [R]25 -251 (c 1.01, CHCl3). IR (KBr): 3024, 2924,
D
1
1612, 1512, 1450. H NMR: 2.31 (6H, s), 2.41 (6H, s), 4.51
(2H, s), 5.33 (2H, s), 6.90-6.91 (4H, m), 7.08-7.11 (8H, m),
7.20-7.24 (8H, m), 7.35-7.36 (6H, m). 13C NMR: 21.10
(CH3), 21.11 (CH3), 64.5 (CH), 74.3 (CH), 127.5 (CH), 128.3
(CH), 128.6 (CH), 129.0 (CH), 129.3 (CH), 129.6 (CH), 129.9
(CH), 133.8 (C), 135.3 (C), 138.0 (C), 138.2 (C), 138.4 (C),
198.2 (C). FABMS m/z: 673 (M - Cl). HRMS-FAB m/z: [M -
Cl]þ calcd for C45H42CuN2, 673.2644; found, 673.2664. Anal.
221 °C (dec): [R]25 -226.7 (c 0.47, CHCl3). IR (KBr): 3063,
D
1589, 1489, 1443, 1265, 1142, 764. 1H NMR: 4.57 (2H, s), 5.40
(2H, s), 6.69 (2H, d, J=9.8), 6.86 (2H, d, J=7.7), 6.99-7.05
(4H, m), 7.09-7.11 (4H, m), 7.12-7.16 (2H, m), 7.19 (2H, d, J=
7.7), 7.30-7.34 (2H, m), 7.41-7.42 (6H, m), 7.46-7.51 (2H, m).
13C NMR: 64.1 (CH), 74.7 (CH), 115.5 (d, J=23, CH), 115.99
(d, J=21, CH), 116.01 (d, J=24, CH), 116.1 (d, J=22, CH),
123.9 (d, J = 2, CH), 124.3 (d, J = 3, CH), 127.5 (CH), 129.7
(CH), 129.8 (CH), 131.1 (d, J=8, CH), 137.2 (C), 138.8 (d, J=6,
C), 139.9 (d, J=7, C), 163.2 (d, J=249, C), 163.3 (d, J=248, C),
199.3 (C). Anal. Calcd for C41H30ClCuF4N2: C, 67.86; H, 4.17;
N, 3.86. Found: C, 67.65; H, 4.31; N, 3.99.
Calcd for C45H43BF4N2 0.55CHCl3: C, 70.55; H, 5.53; N,
3.61. Found: C, 70.40; H, 5.60; N, 3.57.
3
Typical Procedure for the AAAr of Aliphatic Allylic Bromides.
(þ)-(S)-3-Phenyloct-1-ene (γ-3aa)11,21 (Table 1, entry 6). In a
10 mL tube capped with a rubber septum, 1f (14.5 mg, 0.02 mmol)
and 2a (190 mg, 1.0 mmol) were dissolved in CH2Cl2 (2 mL)
and stirred for 10 min at -78 °C. A 3.0 M solution of PhMgBr
(0.40 mL, 1.2 mmol) in Et2O was diluted with CH2Cl2 (0.5 mL)
and added over 30 min to the above mixture using a syringe pump.
After the addition of PhMgBr, the mixture was stirred for 30 min
and diluted with Et2O (6 mL). The reaction was quenched with
10% HCl (1 mL), and the aqueous phase was separated and
extractedwithEt2O(3ꢀ 3mL). Thecombinedorganic layerswere
dried over Na2SO4 and filtered. A small part of the filtrate was
passed through a short plug of silica gel to remove residual metal
and subjected to a GC analysis (DB-1, 30 m ꢀ 0.25 mm: 35 to 160
°C at 5 °C/min) to determine conversion and regioselectivity. The
remainder of the filtrate was concentrated in vacuo and purified by
column chromatography (pentane/Et2O = 1:0-50:1) to give an
84:16 mixture of γ-3aa with 87% ee and R-3aa (176 mg, 93%) as
a colorless oil: [R]20D þ19.8 (c 1.65, CHCl3); lit.11 [R]20D -20.8 (c
1.52, CHCl3) for the R-enantiomer. 1H and 13C NMR, IR, and
MS were identical to those reported.11 Enantioselectivity was deter-
mined by a chiral GC analysis (CP-Chiralsil-Dex-CB, 25 m ꢀ
0.25 mm: 40 °C for 20 min and then to 70 °C at 2 °C/min; major
116.2 min, minor 117.8 min).
[(4S,5S)-1,3-Bis(bis(2-fluorophenyl)methyl)-4,5-diphenylimi-
dazolidin-2-ylidene]copper(I) Chloride (1h). Column chromatog-
raphy (benzene to CHCl3/EtOH=19:1) gave the title compound
as a pale yellow, amorphous solid (206 mg, 94%) of mp 87-
89 °C: [R]25 -160.0 (c 1.00, CHCl3). IR (KBr): 3040, 2908,
D
1589, 1489, 1450, 1273, 1219, 756. 1H NMR: 4.73 (2H, s), 5.92
(2H, s), 6.94-6.98 (2H, m), 7.02-7.15 (10H, m), 7.28-7.36
(10H, m), 7.40-7.48 (4H, m). 13C NMR: 53.0 (CH), 75.7 (CH),
115.7 (d, J=22, CH), 115.9 (d, J=22, CH), 123.9 (d, J=13, C),
124.3 (d, J=13, C), 125.1 (d, J=3, CH), 125.3 (d, J=3, CH),
128.3 (CH), 129.0 (CH), 129.3 (CH), 129.5 (d, J=3, CH), 130.5
(d, J=3, CH), 130.6 (d, J=8, CH), 130.9 (d, J=8, CH), 136.3
(C), 160.3 (d, J = 249, C), 160.7 (d, J = 249, C), 197.5 (C).
FABMS m/z: 689 (M - Cl). HRMS-FAB m/z: [M - Cl]þ calcd
for C41H30CuF4N2, 689.1641; found, 689.1639. Anal. Calcd for
C41H30ClCuF4N2 0.5CHCl3: C, 63.47; H, 3.91; N, 3.57. Found:
3
C, 63.35; H, 3.97; N, 3.65.
[(4S,5S)-1,3-Bis(bis(3,5-difluorophenyl)methyl)-4,5-diphenyli-
midazolidin-2-ylidene]copper(I) Chloride (1i). Column chroma-
tography (benzene to CHCl3/EtOH = 30:1) gave the title
compound as a white, amorphous solid (219 mg, 92%) of mp
(þ)-(S)-3-Phenylhex-1-ene (γ-3ba)22 (Table 1, entry 13). The
typical procedure with column chromatography (pentane/
Et2O = 1:0-50:1) gave a 91:9 mixture of γ-3ba with 74% ee
and R-3ba (98%) as a colorless oil: [R]20D þ34.8 (c 1.19, CHCl3).
IR (neat): 3071, 3024, 2955, 2924, 1636, 1597, 1489, 1458, 1373,
995, 910, 764. 1H NMR: 0.89 (3H, t, J=7.3), 1.19-1.34 (2H, m),
1.63-1.74 (2H, m), 3.25 (1H, dt, J=7.6, 7.6), 5.00 (1H, m), 5.02
(1H, m), 5.95 (1H, ddd, J=7.6, 10.4, 18.0), 7.17-7.20 (3H, m),
7.28-7.31 (2H, m). 13C NMR: 13.9 (CH3), 20.6 (CH2), 37.6
(CH2), 49.6 (CH), 113.8 (CH2), 126.1 (CH), 127.6 (CH), 128.4
(CH), 142.6 (CH), 144.7 (C). EIMS m/z: 161 (M þ 1, 2%), 160
(Mþ, 7%), 159 (M - 1, 9%), 131 (24), 117 (97), 105 (32), 84 (100).
Enantioselectivity was determined by a chiral GC analysis (CP-
Chiralsil-Dex-CB, 25 m ꢀ 0.25 mm: 70 °C for 25 min and then to
120 °C at 10 °C/min; major 22.8 min, minor 23.3 min).
229-231 °C (dec): [R]25 -205.9 (c 0.84, CHCl3). IR (KBr):
D
3062, 1620, 1597, 1443, 1327, 1203, 1119, 995, 856, 702. 1H
NMR: 4.57 (2H, s), 5.38 (2H, s), 6.55 (4H, d, J=5.5), 6.80-6.86
(6H, m), 6.90-6.94 (2H, m), 7.10-7.12 (4H, m), 7.47-7.49
(6H, m). 13C NMR: 63.6 (CH), 74.8 (CH), 105.1 (t, J=25, CH),
105.2 (t, J=25, CH), 111.3 (dd, J=7.2, 21, CH), 112.0 (dd, J=
7.2, 21, CH), 127.3 (CH), 130.1 (CH), 130.2 (CH), 136.4 (C),
139.5 (t, J=8.3, C), 140.3 (t, J=8.3, C), 163.6 (dd, J=12.4, 252,
C), 163.8 (dd, J = 13.5, 251, C), 199.6 (C). FABMS m/z: 761
(M-Cl). HRMS-FAB m/z: [M - Cl]þ calcd for C41H26CuF8N2,
761.1264; found, 761.1273. Anal. Calcd for C41H26ClCuF8N2
0.5CHCl3: C, 58.14; H, 3.12; N, 3.27. Found: C, 58.09; H, 3.29;
N, 3.27.
3
[(4S,5S)-1,3-Bis(bis(4-trifluoromethylphenyl)methyl)-4,5-diph-
enylimidazolidin-2-ylidene]copper(I) Chloride (1j). Column
chromatography (benzene to CHCl3/EtOH = 20:1) gave the
title compound as a beige solid (231 mg, 83%) of mp 227-229
°C (dec): [R]25D -214.2 (c 0.29, CHCl3). IR (KBr): 3070, 1620,
1420, 1327, 1165, 1126, 1065, 818. 1H NMR: 4.57 (2H, s), 5.59
(21) (a) Mixer, R. Y.; Young, W. G. J. Am. Chem. Soc. 1956, 78, 3379–
€
3384. (b) Dubner, F.; Knochel, P. Tetrahedron Lett. 2000, 41, 9233–9237.
(22) Miyaura, N.; Itoh, M.; Suzuki, A. Bull. Chem. Soc. Jpn. 1977, 50,
2199–2200.
J. Org. Chem. Vol. 76, No. 5, 2011 1405

Selim et al.
JOCArticle
(þ)-(R)-2-Cyclohexyl-2-phenylprop-1-ene (γ-3ca) (Table 1,
entry 17). The typical procedure was performed in half-scale
(0.5 mmol of 2c). The Grignard reagent was diluted with CH2Cl2
(0.25 mL) and added over 15 min. Column chromatography
(pentane) gave an 89:11 mixture of γ-3ca with 93% ee and R-3ca
(97%) as a colorless oil: [R]21D þ63.9 (c 1.33, CHCl3). IR (neat):
EIMS m/z: 218 (Mþ), 147. HRMS-EI m/z: [M]þ calcd for
C15H22O, 218.1671; found, 218.1674. Enantioselectivity was
determined after conversion to the corresponding terminal
alcohol by hydroboration-oxidation (vide infra).
(þ)-(S)-3-(4-Chlorophenyl)oct-1-ene (γ-3ad) (Table 2, entry
7). Modification of the typical procedure, as in Table 2, entry 4,
and column chromatography (pentane) gave an 87:13 mixture
of γ-3ad with 80% ee and R-3ad (98%) as a pale yellow oil.
1
3024, 2924, 2855, 1636, 1597, 1490, 1450, 1381, 910, 702. H
NMR: 0.76-1.91 (11H, m), 2.92 (1H, dd, J=9.2, 9.2), 4.98-
5.02 (2H, m), 5.97 (1H, dt, J = 9.2, 17.4), 7.14-7.19 (3H, m),
7.25-7.29 (2H, m). 13C NMR: 26.3 (CH2), 26.5 (CH2), 31.26
(CH2), 31.30 (CH2), 42.1(CH), 57.6 (CH), 114.9 (CH2), 126.0
(CH), 128.0 (CH), 128.4 (CH), 141.3 (CH), 144.2 (C). EIMS m/z:
201 (M þ 1), 200 (Mþ). HRMS-EI m/z: [M]þ calcd for C15H20,
200.1565; found, 200.1570. Enantioselectivity was determined
by a chiral GC analysis (CP-Chiralsil-Dex-CB, 25 m ꢀ 0.25 mm:
40 °C for 10 min, to 100 °C at 1 °C/min, 100 °C for 30 min, and to
170 °C at 5 °C/min; minor 94.4 min, major 95.3 min).
1
Regioselectivity was determined by the integration area of H
NMR signals at 5.46-5.55 ppm for R-3ad and 5.90 ppm for γ-
3ad: [R]25D þ29.1 (c 1.14, CHCl3). IR (neat): 2924, 2855, 1489.
1H NMR: 0.85 (3H, t, J=6.6), 1.15-1.31 (6H, m), 1.60-1.72
(2H, m), 3.21 (1H, dt, J=7.6, 7.6), 5.00 (1H, d, J=17.5), 5.02
(1H, d, J=10.4), 5.90 (1H, ddd, J=7.6, 10.4, 17.5), 7.10-7.12
(2H, m), 7.25-7.27 (2H, m). 13C NMR: 14.0 (CH3), 22.5 (CH2),
27.1 (CH2), 31.7 (CH2), 35.3 (CH2), 49.2 (CH), 114.2 (CH2), 128.5
(CH), 128.9 (CH), 131.7 (C), 142.0 (CH), 143.1 (C). EIMS m/z: 224
(M þ 2), 222 (Mþ), 187 (M - Cl), 151. HRMS-EI m/z: [M]þ calcd
for C14H19Cl, 222.1175; found, 222.1166. Enantioselectivity was
determined by chiral GC analysis (CP-Chiralsil-Dex-CB, 25 m ꢀ
0.25 mm: 100 °C; minor 57.7 min, major 59.2 min).
(þ)-(R)-4,4-Dimethyl-3-phenylpent-1-en (γ-3da)23 (Table 1,
entry 20). Modification of the typical procedure, as in Table 1,
entry 17, and column chromatography (pentane) gave a 53:47
mixture of γ-3da with 87% ee and R-3da (61%) as a volatile pale
yellow oil: [R]25D þ45.3 (c 0.67, CDCl3); lit.23 [R]25D þ101 (neat)
for optically pure (R)-γ-3da. IR (neat): 3063, 3024, 2955, 1636,
1605, 1458, 1366, 972, 910, 741. 1H NMR: 0.89 (9H, s), 3.02 (1H,
dd, J=0.7, 9.8), 5.03 (1H, ddd, J=0.7, 2.1, 16.8), 5.08 (1H, dd,
J=2.1, 10.1), 6.26 (1H, ddd, J=9.8, 10.1, 16.8), 7.16-7.20 (5H,
m). 13C NMR: 28.0 (CH3), 33.8 (C), 61.5 (CH), 116.2 (CH2),
126.0 (CH), 127.9 (CH), 129.2 (CH), 138.9 (CH), 142.9 (C).
EIMS m/z: 175 (M þ 1, 1%), 174 (Mþ, 4%), 131 (7), 117 (30),
91 (15), 84 (100). Enantioselectivity was determined by chiral
GC analysis (CP-Chiralsil-Dex-CB, 25 m ꢀ 0.25 mm: 90 °C
for 30 min and then to 160 °C at 5 °C/min; minor 9.8 min, major
10.5 min).
(þ)-(S)-3-(4-Fluorophenyl)oct-1-ene (γ-3ae) (Table 2, entry
10). Modification of the typical procedure, as in Table 2, entry
4, and column chromatography (pentane) gave an 88:12 mixture
of γ-3ae with 66% ee and R-3ae (96%) as a pale yellow oil.
1
Regioselectivity was determined by the integration area of H
NMR signals at 5.46-5.55 ppm for R-3ae and 5.91 ppm for γ-
3ae: [R]25D þ18.1 (c 1.34, CHCl3). IR (neat): 2924, 2862, 1512,
1227. 1H NMR: 0.85 (3H, t, J = 6.3), 1.16-1.31 (6H, m),
1.65-1.70 (2H, m), 3.21 (1H, dt, J = 7.5, 7.5), 4.99 (1H, m),
5.01 (1H, m), 5.91 (1H, ddd, J=7.5, 10.4, 17.2), 6.94-7.00 (2H,
m), 7.11-7.15 (2H, m). 13C NMR: 14.0 (CH3), 22.6 (CH2), 27.1
(CH2), 31.8 (CH2), 35.5 (CH2), 49.1 (CH), 113.9 (CH2), 115.1
(d, J=20, CH), 128.9 (d, J=7, CH), 140.2 (d, J=2, C), 142.4
(CH), 161.3 (d, J=244, C). EIMS m/z: 207 (M þ 1), 206 (Mþ),
135. HRMS-EI m/z: [M]þ calcd for C14 H19 F, 206.1471; found,
206.1476. Enantioselectivity was determined by chiral GC anal-
ysis (CP-Chiralsil-Dex-CB, 25 m ꢀ 0.25 mm: 100 °C; minor 17.6
min, major 18.2 min).
(þ)-(S)-3-p-Tolyloct-1-ene (γ-3ab) (Table 2, entry 4). The
typical procedure was performed in half-scale (0.5 mmol of
2a). The Grignard reagent was diluted with CH2Cl2 (0.4 mL)
and added over 1 h. Column chromatography (pentane) gave an
82:18 mixture of γ-3ab with 84% ee and R-3ab (92%) as a pale
yellow oil. Regioselectivity was determined by the integration
area of 1H NMR signals at 5.46-5.57 ppm for R-3ab and
(þ)-(S)-3-(3-Fluorophenyl)oct-1-ene (γ-3af) (Table 2, entry
12). Modification of the typical procedure, as in Table 2, entry
4, and column chromatography (pentane) gave a 79:21 mixture
of γ-3af with 52% ee and R-3af (96%) as a pale yellow oil.
5.92 ppm for γ-3ab: [R]25 þ27.0 (c 1.03, CHCl3). IR (neat):
D
2924, 2862, 1512, 1458. 1H NMR: 0.84-0.90 (3H, m), 1.21-1.32
(6H, m), 1.63-1.70 (2H, m), 2.32 (3H, s), 3.19 (1H, dt, J=7.5,
7.5), 4.98 (1H, m), 5.00 (1H, m), 5.92 (1H, ddd, J =7.5, 10.3,
17.5), 7.06-7.11 (4H, m). 13C NMR: 14.1 (CH3), 21.0 (CH3),
22.6 (CH2), 27.2 (CH2), 31.8 (CH2), 35.4 (CH2), 49.5 (CH), 113.6
(CH2), 127.4 (CH), 129.1 (CH), 135.5 (C), 141.7 (C), 142.8 (CH).
EIMS m/z: 202 (Mþ), 131. HRMS-EI m/z: [M]þ calcd for
C15H22, 202.1722; found, 202.1730. Enantioselectivity was de-
termined after conversion to the corresponding terminal alcohol
by hydroboration-oxidation (vide infra).
1
Regioselectivity was determined by the integration area of H
NMR signals at 5.49-5.58 ppm for R-3af and 5.90 ppm for γ-
3af: [R]25D þ13.0 (c 1.29, CHCl3). IR (neat): 2932, 2862, 1589.
1H NMR: 0.86 (3H, t, J=6.9), 1.16-1.31 (6H, m), 1.62-1.72
(2H, m), 3.23 (1H, dt, J=7.5, 7.5), 5.01 (1H, m), 5.04 (1H, m),
5.90 (1H, ddd, J=7.5, 10.7, 18.3), 6.88-6.90 (2H, m), 6.95-6.97
(2H, m). 13C NMR: 14.0 (CH3), 22.5 (CH2), 27.1 (CH2), 31.7
(CH2), 35.3 (CH2), 49.7 (d, J=2, CH), 112.9 (d, J=22, CH),
114.3 (d, J=20, CH), 114.4 (CH2), 123.3 (d, J=2, CH), 129.7 (d,
J=8, CH), 141.8 (CH), 147.3 (d, J=7, C), 163.0 (d, J=245, C).
EIMS m/z: 207 (M þ 1), 206 (Mþ), 135. HRMS-EI m/z: [M]þ
calcd for C14 H19 F, 206.1471; found, 206.1473. Enantioselec-
tivity was determined by chiral GC analysis (Chiraldex B-DM,
25 m ꢀ 0.25 mm ꢀ 0.25 μm: 40 °C for 20 min and then to 70 °C at
1 °C/min; major 146.1 min, minor 148.9 min).
(þ)-(R)-3-Cyclohexyl-3-(4-tolyl)prop-1-ene (γ-3cb) (Table 3,
entry 3). The typical procedure was performed in half-scale (0.5
mmol of 2c). The Grignard reagent was diluted with CH2Cl2
(0.4 mL) and added over 15 min. Column chromatography
(pentane) gave an 87:13 mixture of γ-3cb with 96% ee and R-3cb
(99%) as a colorless oil. Regioselectivity was determined by a
GC analysis (DB-1, 30 m ꢀ 0.25 mm: 35 to 160 °C at 5 °C/min; γ
25.7 min, R 28.3 min). [R]25D þ68.8 (c 1.41, CHCl3). IR (neat):
2924, 2855, 1636, 1512, 1381, 910, 818, 725. 1H NMR: 0.75-1.89
(11H, m), 2.31 (3H, s), 2.89 (1H, dd, J=9.2, 9.2), 4.97-5.01 (2H,
(þ)-(S)-3-(4-Methoxyphenyl)-1-octene (γ-3ac) (Table 2, entry
6). Modification of the typical procedure, as in Table 2, entry 4,
and column chromatography (pentane) gave a 79:21 mixture of
γ-3ac with 79% ee and R-3ac (99%) as a pale yellow oil.
1
Regioselectivity was determined by the integration area of H
NMR signals at 6.82-6.86 ppm for R-3ac and 5.92 ppm for γ-
3ac: [R]25D þ22.0 (c 1.27, CHCl3). IR (neat): 2924, 2855, 1512,
1250. 1H NMR: 0.85 (3H, t, J = 6.9), 1.18-1.31 (6H, m),
1.64-1.69 (2H, m), 3.18 (1H, dt, J = 7.5, 7.5), 3.79 (3H, s),
4.97 (1H, m), 5.00 (1H, m), 5.92 (1H, m), 6.82-6.86 (2H, m),
7.09-7.11 (2H, m). 13C NMR: 14.0 (CH3), 22.5 (CH2), 27.2
(CH2), 31.8 (CH2), 35.4 (CH2), 49.0 (CH), 55.0 (CH3), 113.4
(CH2), 113.7 (CH), 128.4 (CH), 136.6 (C), 142.8 (CH), 157.9 (C).
(23) (a) Lardicci, L.; Menicagli, R. J. Org. Chem. 1972, 37, 1060–1062.
(b) Caporusso, A. M.; Zampieri, A.; Aronica, L. A.; Banti, D. J. Org. Chem.
2006, 71, 1902–1910.
1406 J. Org. Chem. Vol. 76, No. 5, 2011

Selim et al.
JOCArticle
m), 5.95 (1H, m), 7.03-7.10 (4H, m). 13C NMR: 20.9 (CH3),
26.3 (CH2), 26.5 (CH2), 31.3 (CH2), 42.0 (CH), 57.1 (CH), 114.6
(CH2), 127.8 (CH), 129.1 (CH), 135.4 (C), 141.2 (C), 141.5 (CH).
EIMS m/z: 215 (M þ 1), 214 (Mþ). HRMS-EI m/z: [M]þ calcd
for C16H22, 214.1722; found, 214.1716. Enantioselectivity was
determinedby a chiralGC analysis (CP-Chiralsil-Dex-CB, 25 mꢀ
0.25 mm; 40 °C for 30 min, to 100 °C at 1 °C/min, 100 °C for
70 min, and then to 170 °C at 5 °C/min; minor 149.4 min, major
151.0 min).
(þ)-(R)-3-(4-Chlorophenyl)-3-cyclohexylprop-1-ene (γ-3cd)
(Table 3, entry 5). Modification of the typical procedure, as in
Table 3, entry 3, and column chromatography (pentane) gave a
96:4 mixture of γ-2cd with 93% ee and R-2cd (97%) as colorless
oil. Regioselectivity was determined by a GC analysis (DB-1, 30
m ꢀ 0.25 mm: 35 to 160 °C at 5 °C/min; γ 28.4 min, R 32.0 min).
[R]25D þ77.1 (c 1.72, CHCl3). IR (neat): 2924, 2855, 1636, 1489,
1450, 1096, 910, 826. 1H NMR: 0.74-1.88 (11H, m), 2.91 (1H,
dd, J=9.2, 9.2), 4.97-5.03 (2H, m), 5.92 (1H, ddd, J=9.2, 10.1,
16.8), 7.07-7.26 (4H, m). 13C NMR: 26.3 (CH2), 26.4 (CH2),
31.16 (CH2), 31.19 (CH2), 42.1 (CH), 56.8 (CH), 115.3 (CH2),
128.5 (CH), 129.3 (CH), 131.6 (C), 140.7 (CH), 142.6 (C). EIMS
m/z: 235 (M þ 1), 234 (Mþ). HRMS-EI m/z: [M]þ calcd for
C15H19Cl, 234.1175; found, 234.1184. Enantioselectivity was
determinedby a chiralGC analysis (CP-Chiralsil-Dex-CB, 25 mꢀ
0.25 mm: 40 °C for 30 min, to 100 °C at 1 °C/min, 100 °C for
70 min, and then to 170 °C at 5 °C/min; minor 171.2 min, major
171.4).
(þ)-(R)-3-Cyclohexyl-3-(4-fluorophenyl)prop-1-ene (γ-3ce)
(Table 3, entry 6). Modification of the typical procedure, as in
Table 3, entry 3, and column chromatography (pentane) gave a
95:5 mixture of γ-3ce with 92% ee and R-3ce (98%) as a colorless
oil. Regioselectivity was determined by a GC analysis (DB-1, 30
m ꢀ 0.25 mm: 35 to 160 °C at 5 °C/min; γ 23.5 min, R 25.7 min).
[R]25D þ58.1 (c 1.84, CHCl3). IR (neat): 2924, 2855, 1636, 1512,
1381, 1227, 1157, 910, 833. 1H NMR: 0.74-1.89 (11H, m), 2.92
(1H, dd, J=9.2, 9.2), 4.97-5.02 (2H, m), 5.92 (1H, ddd, J=9.2,
10.1, 16.8), 6.94-7.13 (4H, m). 13C NMR: 26.3 (CH2), 26.4
(CH2), 31.2 (CH2), 42.2 (CH), 56.6 (CH), 115.0 (CH2), 115.1
(CH, d, J=21), 129.2 (CH, d, J=7.3), 139.8 (C, d, J=3.1), 141.0
(CH), 161.3 (C, d, J=244). EIMS m/z: 219 (M þ 1), 218 (Mþ).
HRMS-EI m/z: [M]þ calcd for C15H19F, 218.1471; found,
218.1467. Enantioselectivity was determined by a chiral GC
analysis (CP-Chiralsil-Dex-CB, 25 m ꢀ 0.25 mm: 40 °C for 30
min, to 100 °C at 1 °C/min, 100 °C for 55 min, and then to 170 °C
at 5 °C/min; minor 125.5 min, major 127.5 min).
for 70 min, and then to 150 °C at 1 °C/min; minor 270.0 min,
major 270.4 min).
(þ)-(R)-3-Cyclohexyl-3-(3,4-methylenedioxyphenyl)prop-1-ene
(γ-3ch) (Table 3, entry 8). Modification of the typical procedure,
as in Table 3, entry 7, and column chromatography (pentane/
Et2O=1:0-50:1) gave a 91:9 mixture of γ-3ch with 93% ee and
R-3ch (41%) as a colorless oil. Regioselectivity was determined
by a GC analysis (DB-1, 30 m ꢀ 0.25 mm: 35 to 200 °C at
5 °C/min; γ 31.2 min, R 33.3 min). [R]25D þ64.9 (c 0.89, CHCl3).
IR (neat): 2924, 2855, 1636, 1489, 1443, 1242, 1042, 936, 810. 1H
NMR: 0.74-1.88 (11H, m), 2.84 (1H, dd, J=9.2, 9.2), 4.98 (1H,
d, J=17), 4.99 (1H, d, J=11), 5.87-5.95 (1H, m), 5.91 (2H, s),
6.58 (1H, dd, J=1.5, 7.9), 6.65 (1H, d, J=1.5), 6.72 (1H, d, J=
7.9). 13C NMR: 26.3 (CH2), 26.5 (CH2), 31.2 (CH2), 31.3 (CH2),
42.1 (CH), 57.2 (CH), 100.8 (CH2), 108.09 (CH), 108.13 (CH),
114.7 (CH2), 120.9 (CH), 138.1 (C), 141.3 (CH), 145.7 (C), 147.6
(C). EIMS m/z: 244 (Mþ). HRMS-EI m/z: [M]þ calcd for
C16H20O2, 244.1463; found, 244.1462. Enantioselectivity was
determined after conversion to the corresponding terminal
alcohol by hydroboration-oxidation (vide infra).
Determination of Enantioselectivity and Absolute Configura-
tion. Absolute Configuration of γ-3ca. (þ)-(R)-3-Cyclohexyl-3-
phenylpropan-1-ol (4) (ref 24). To a solution of a mixture of R-
and γ-3ca (60 mg, 0.3 mmol) in THF (2 mL) cooled in an ice/
water bath was added a 0.5 M solution of 9-BBN (0.9 mL, 0.45
mmol) in THF. The mixture was stirred for 6 h and then allowed
to reach rt. To the mixture were added sequentially EtOH
(1.5 mL), 1 M NaOH (1.5 mL), and 30% H2O2 (1.2 mL). The
mixture was stirred vigorously for 5 h, and then the reaction was
quenched with 10% Na2S2O3 (4 mL). The mixture was diluted
with CH2Cl2 (20 mL), and the aqueous phase was separated and
extracted with CH2Cl2 (2 ꢀ 20 mL). The combined organic
layers were dried over anhydrous Na2SO4, filtered, and con-
centrated in vacuo. Column chromatography (pentane/Et2O=
3:1) gave 4 (58 mg, 89%) as a pale yellow oil: [R]22 þ12.7 (c
D
0.95, pentane); lit.24 [R]22 þ12.4 (c 1.17, pentane). IR (neat):
D
3341(br), 2924, 2855, 1450, 1049, 702. 1H NMR: 0.77-1.84
(12H, m), 1.92 (1H, m), 2.09 (1H, m), 2.45 (1H, m), 3.38 (1H, m),
3.47 (1H, m), 7.12-7.13 (2H, m), 7.19 (1H, m), 7.28-7.29 (2H,
m). 13C NMR: 26.4 (CH2), 26.5 (CH2), 31.0 (CH2), 31.2 (CH2),
35.5 (CH2), 43.2 (CH), 48.6 (CH), 61.7 (CH2), 126.1 (CH), 128.2
(CH), 128.5 (CH), 143.9 (C). EIMS m/z: 219 (M þ 1, 2%), 218
(Mþ, 14%), 136 (21), 118 (100), 105 (73), 91 (87).
Enantioselectivity of γ-3ab. (-)-(S)-3-p-Tolyloctan-1-ol (5).
The above procedure and column chromatography (hexane/
EtOAc = 14:1) gave 5 (89% from γ-3ab with 88% ee) as a
colorless oil: [R]22D -4.14 (c 0.70, CHCl3). IR (neat): 3333, 2924,
(þ)-(R)-3-Cyclohexyl-3-(3,4-dichlorophenyl)prop-1-ene (γ-3cg)
(Table 3, entry 7). The typical procedure was performed in half-
scale (0.5 mmol of 2c). The Grignard reagent was diluted with
CH2Cl2 (0.4 mL) and added over 1 h. Column chromatography
(pentane) gave a 96:4:19 mixture of γ-3cg with 86% ee (81%),
R-3cg (3%), and 2c (16%) as a pale yellow oil. Regioselectivity
was determined by a GC analysis (DB-1, 30 m ꢀ 0.25 mm: 35 to
160 °C at 5 °C/min; γ 36.2 min, R 41.7 min). A mixture of γ- and
R-3cg (99 mg, 74%) was separated from 2c by column chroma-
tography (pentane/Et2O = 1:0-10:1) after treatment with
CaCO3 in refluxing water/dioxane to convert 2c into the corre-
sponding alcohol: [R]25D þ65.1 (c 1.20, CHCl3). IR (neat): 2924,
1
2862, 1512, 1458, 1049, 818. H NMR: 0.83 (3H, t, J = 6.9),
1.07-1.25 (7H, m), 1.52-1.64 (2H, m), 1.77 (1H, m), 1.92 (1H,
m), 2.32 (3H, s), 2.63 (1H, tt, J=5.4, 9.2), 3.44-3.55 (2H, m),
7.04-7.06 (2H, m), 7.09-7.11 (2H, m). 13C NMR: 14.1 (CH3),
21.0 (CH3), 22.5 (CH2), 27.2 (CH2), 31.9 (CH2), 37.0 (CH2), 39.7
(CH2), 42.1 (CH), 61.3 (CH2), 127.4 (CH), 129.1 (CH), 135.5
(C), 142.1 (C). EIMS m/z: 221 (M þ 1), 220 (Mþ), 175, 149.
HRMS-EI m/z: [M]þ calcd for C15H24O, 220.1827; found,
220.1823. Enantioselectivity was determined by a chiral GC
analysis (Betadex 120, 25 m ꢀ 0.25 mm: 130 °C; minor 98.8 min,
major 101.4 min).
1
2855, 1636, 1466, 1389, 1134, 918, 818. H NMR: 0.76-1.87
Enantioselectivity of γ-3ac. (-)-(S)-3-(4-Methoxyphenyl)-
octan-1-ol (6). The above procedure and column chromatog-
raphy (hexane/EtOAc=9:1) gave 6 (98% from γ-3ac with 85%
(11H, m), 2.90 (1H, dd, J=9.2, 9.2), 5.01 (1H, dd, J=1.5, 16.8),
5.04 (1H, dd, J=1.5, 10.1), 5.89 (1H, ddd, J=9.2, 10.1, 16.8),
6.98 (1H, dd, J=2.2, 8.3), 7.23 (1H, d, J=2.2), 7.34 (1H, d, J=
8.3). 13C NMR: 26.2 (CH2), 26.3 (CH2), 31.0 (CH2), 31.2 (CH2),
42.0 (CH), 56.6 (CH), 115.9 (CH2), 127.4 (CH), 129.8 (C), 129.9
(CH), 130.3 (CH), 132.3 (C), 140.0 (CH), 144.5 (C). EIMS m/z:
272 (M þ 4), 270 (M þ 2), 268 (Mþ). HRMS-EI m/z: [M]þ calcd
for C15H18Cl2, 268.0786; found, 268.0783. Enantioselectivity
was determined by a chiral GC analysis (CP-Chiralsil-Dex-CB,
25 m ꢀ 0.25 mm: 40 °C for 30 min, to 100 °C at 0.5 °C/min, 100 °C
ee) as a colorless oil: [R]25 -5.78 (c 0.65, CHCl3). IR (neat):
D
3348, 2923, 2855, 1512, 1232, 1034, 826. 1H NMR: 0.83 (3H, t,
J=6.8), 1.12-1.30 (7H, m), 1.50-1.63 (2H, m), 1.75 (1H, m),
1.92 (1H, m), 2.62 (1H, tt, J=5.2, 9.5), 3.43-3.55 (2H, m), 3.79
(3H, s), 6.83-6.85 (2H, m), 7.06-7.09 (2H, m). 13C NMR: 14.1
(24) Murakata, M.; Tsutsui, H.; Hoshino, O. Org. Lett. 2001, 3, 299–302.
J. Org. Chem. Vol. 76, No. 5, 2011 1407

Selim et al.
JOCArticle
(CH3), 22.5 (CH2), 27.1 (CH2), 31.9 (CH2), 37.1 (CH2), 39.8
(CH2), 41.6 (CH), 55.2 (CH3), 61.3 (CH2), 113.8 (CH), 128.4
(CH), 137.2 (C), 157.8 (C). EIMS m/z: 237 (M þ 1), 236 (Mþ),
191, 165. HRMS-EI m/z: [M]þ calcd for C15H24O2, 236.1776;
found, 236.1778. Enantioselectivity was determined by a
chiral GC analysis (Betadex 120, 25 m ꢀ 0.25 mm: 130 °C for
200 min and then to 150 °C at 1 °C/min; minor 232.9 min,
major 235.6 min).
CHCl3). IR (neat): 3356, 2924, 2855, 1489, 1242, 1042. 1H NMR:
0.77-2.07 (14H, m), 2.37 (1H, m), 3.39 (1H, m), 3.48 (1H, m), 5.93
(2H, s), 6.56 (1H, dd, J=7.9, 1.8), 6.63 (1H, d, J=1.8), 6.72 (1H, d,
J=7.9). 13C NMR: 26.46 (CH2), 26.50 (CH2), 26.52 (CH2), 31.0
(CH2), 31.3 (CH2), 35.7 (CH2), 43.3 (CH), 48.4 (CH), 61.6 (CH2),
100.8 (CH2), 107.9 (CH), 108.2 (CH), 121.5 (CH), 137.8 (C), 145.7
(C), 147.6 (C). EIMS m/z: 263 (M þ 1), 262 (Mþ), 179. HRMS-EI
m/z: [M]þ calcd for C16H22O3, 262.1569; found, 262.1569. En-
antioselectivity was determined by a chiral HPLC analysis
(Chiralpak AD-H: hexane/i-PrOH = 98:2; 1 mL/min; 254 nm;
major 35.2 min, minor 43.4 min).
Enantioselectivity of γ-3ch. (R)-3-Cyclohexyl-3-(3,4-methyl-
enedioxyphenyl)propan-1-ol (7). To a solution of the 91:9 mixture
of γ- and R-3ch (24 mg, 0.10 mmol) in THF (0.8 mL) cooled in
an ice/water bath was added a 0.5 M solution of 9-BBN in THF
(0.3 mL, 0.15 mmol). After the cooling bath was removed, the
mixture was stirred for 10 h at rt, and then EtOH (0.6 mL), aqueous
1 M NaOH (0.6 mL), and aqueous 30% H2O2 (0.5 mL) were
sequentially added. The mixture was stirred vigorously for 5 h, and
then the reaction was quenched with 10% Na2S2O3 (4 mL). The
mixture was diluted with Et2O (5 mL), and the aqueous phase was
separated and extracted with Et2O (3 ꢀ 10 mL). The combined
organic layers were dried over Na2SO4, filtered, and concentrated
in vacuo. Column chromatography (hexane/EtOAc=3:1) gave 7(5
Acknowledgment. This research was partially supported by
a Grant-in-Aid for Young Scientist (B) and a Grant-in-Aid for
Scientific Research (A) from the Japan Society for the Promo-
tion of Science (JSPS), and Targeted Protein Research Pro-
gram from Japan Science and Technology Agency (JST).
Supporting Information Available: NMR charts of the
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
mg, 19%) with 93% ee as a colorless oil: [R]25 -3.74 (c 0.12,
D
1408 J. Org. Chem. Vol. 76, No. 5, 2011